Browsing by Author "Shripad B. Deshpande"

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3-Nitropropionic acid-induced depression of spinal reflexes does not involve 5-hydroxytryptaminergic system in contrast to ischemia-induced depression in neonatal rat spinal cord in vitro
(2008) Rajesh Gupta; Archana Jha; Shripad B. Deshpande
The involvement of 5-hydroxytryptaminergic (5-HTergic) system for the 3-nitropropionic acid (3-NPA)-induced depression of spinal reflexes was evaluated and compared with other energy deficiency condition (ischemia; glucose-free and O2-free). The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials were recorded at ventral root by stimulating the corresponding dorsal root in neonatal rat spinal cord in vitro. Superfusion of 3-NPA (3.4 mM) or ischemic solution depressed the reflexes in a time-dependent manner abolishing them by 35 min. Pretreatment with pindolol (1 μM), ketanserin (10 μM) or ondansetron (0.1 μM); 5-HT1, 5-HT2, or 5-HT3 receptor antagonist, respectively, did not block the 3-NPA-induced depression of reflexes whereas, ischemia-induced depression was blocked by ondansetron. 5-HT content of the spinal cords incubated with 3-NPA (3.4 mM) for 30 min was decreased significantly (33 ng/g tissue) while increased (286 ng/g) in cords exposed to ischemic solution as compared to saline-treated cords (161 ng/g). Thus, 3-NPA-induced depression of spinal reflexes does not involve 5-HTergic pathway unlike ischemia-induced depression. © 2008 Elsevier Ireland Ltd. All rights reserved.
3-Nitropropionic acid-induced depression of spinal reflexes involves mechanisms different from ischemia-induced depression
(2008) Rajesh Gupta; Shripad B. Deshpande
Effect of 3-nitropropionic acid (3-NPA) and ischemia (glucose- and O2-free solution) on synaptic transmission in hemisected spinal cord from 4 to 8 day old rats was examined in vitro. Stimulation of a dorsal root (L3-5 segments) evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root. Superfusion of 3-NPA (0.17-3.4 mM) depressed the reflexes in a concentration- and time-dependent manner. At 3.4 mM of 3-NPA, the reflexes were abolished by 35 min. Time required to produce 50% depression (T-50) was around 170, 80, 40 and 17 min for MSR and 110, 70, 25 and 16 min for PSR at 0.17, 0.51, 1.7 and 3.4 mM of 3-NPA, respectively. Ischemia also produced a time-dependent depression of reflexes and abolished them by 35 min and the T-50 values were around 18 min. Presence of creatine phosphate (10 mM) in the superfusing medium did not alter the time course of 3-NPA-induced depression of reflexes but prolonged the ischemia-induced depression. dl-2-amino-5-phosphonovaleric acid (NMDA receptor antagonist; 10 μM) failed to block the 3-NPA (3.4 mM)-induced depression of reflexes, but blocked the ischemia-induced depression. The results indicate that 3-NPA-induced depression of spinal reflexes does not involve NMDA receptors and is different from ischemia-induced depression. © 2008 Elsevier Inc. All rights reserved.
5-HT-induced depression of the spinal monosynaptic reflex potential utilizes different types of 5-HT receptors depending on Mg2+ availability
(Polish Academy of Sciences, 2009) Shripad B. Deshpande; Amar N. Maurya; Jitendra N. Singh
Receptor subtypes involved in the 5-hydroxytryptamine (5-HT)-induced depression of synaptic transmission in neonatal rat spinal cords in vitro were evaluated in the absence or presence of Mg2+ in the medium. Stimulation of a dorsal root evoked monosynaptic reflex potential (MSP) and polysynaptic reflex potential (PSP) in the segmental ventral root in Mg2+-free medium where the voltage-dependent blockade of NMDA receptors is absent. The 5-HT (0.3-50 μM) in the Mg2+-free medium depressed the MSP and PSP in a concentration-dependent manner. At 30 μM of 5-HT, the depression was 57% and 95% for MSP and PSP, respectively, and no further depression was seen at 50 μM. The 5-HT-induced depression of the reflexes in the Mg2+-free medium was blocked by ondansetron (5-HT3 receptor antagonist), but not by spiperone (5-HT2A/2C antagonist). In the Mg2+-free medium, phenylbiguanide (5-HT3 agonist) also depressed the MSP and PSP in a concentration-dependent manner and was blocked by ondansetron. Addition of Mg2+ (1.3 mM) to the medium abolished the PSP and decreased the MSP by 30%. In the presence of Mg2+, 5-HT (1-50 μM) also depressed the MSP in a concentration-dependent manner. At 10 μM of 5-HT, there was approximately 20% depression and at 50 μM the depression was 100%. The 5-HT-induced depression of MSP in the Mg2+-containing medium was antagonized by spiperone (p < 0.05, two-way ANOVA), but not by ondansetron. The results indicate that the 5-HT-induced depression of MSP involves 5-HT3 receptors in the Mg2+-free medium and 5-HT2A/ 2C in the presence of Mg2+ when NMDA receptors are in the closed state. Copyright © 2009 by Institute of Pharmacology Polish Academy of Sciences.
Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier: Involvement of dopamine toxicity
(1997) Hitoo Nishino; Michiko Kumazaki; Atsuo Fukuda; Ichiro Fujimoto; Yasunobu Shimano; Hideki Hida; Terumi Sakurai; Shripad B. Deshpande; Hideo Shimizu; Shigehiro Morikawa; Toshiro Inubushi
Mechanisms underlying the selective vulnerability of the lateral striatal area to the toxic effects of 3-nitropropionic acid (3-NPA) were investigated in rats. A single exposure to 3-NPA (20 mg/kg, s.c.) induced no deficits in behavior and histology, but subsequent injection produced motor symptoms, catalepsy, lip smacking, abnormal gait, paddling, rolling, opisthotonos, tremor, recombence, somnolence and so on, in 30% of the animals within a few hours. Diffusion-weighted magnetic resonance imaging of the brains revealed an area of high signal intensity in the bilateral striata. By this stage (within a few hours), striatal astrocytes had become swollen and disintegrated. Extravasation of immunoglobulin G was detected, indicating blood-brain barrier (BBB) dysfunction. Electron microscopy revealed edema and disorganization of structures inside the astrocytic end-feet around the branches of the lateral striatal artery. Neurons were less vulnerable than astrocytes to the 3-NPA injury. Treatment of the rats with D2 receptor agonist prior to exposure to 3-NPA attenuated the behavioral abnormalities and histological damage whereas pretreatment with D2 antagonist exacerbated these changes. The concentrations of extracellular dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) were both increased in rats exposed to 3-NPA. In vitro imaging of astrocytes revealed a progressive increase in [Ca2+](i) after superfusion with 3-NPA, and the 'ceiling' level was maintained even after extensive washing. DA superfusion also increased the astrocytic [Ca2+](i) and this increase was reversible. Data indicate that 3-NPA-induced striatal damage was associated with astrocytic cell death and dysfunction of the BBB. Intracellular edema and extreme Ca2+ overload induced by the toxin were further aggravated by an increase in the level of DA activity. These factors acting either singly or in combination may trigger astrocyte destruction.
Acute toxicity of bisphenol a in rats
(2012) Jayanti Pant; Shripad B. Deshpande
Bisphenol A (BPA), an estrogenic compound, is used in manufacturing plastics and is known to produce toxic effects on various systems in man and animals. Since the use of plastics in day-to-day life is increasing, exposure to BPA will also increase. Therefore, this study was undertaken to determine the median lethal dose (LD50) of BPA via intraperitoneal and intravenous route in adult rats (by Dixon's up and down method) and also to know the acute systemic changes (in blood pressure, respiration and ECG) produced by lethal dose of BPA. Adult female albino rats of Charles Foster strain were used in the study. LD50 of BPA was 841 and 35.26 mg/kg body weight for ip and iv route, respectively. Injection of lethal dose of BPA (40 mg/kg body weight) produced acute toxicity manifesting as immediate respiratory arrest and hypotension after the injection of BPA followed by bradycardia. The animals died within 7.3 ± 0.7 min. Volume of ethanol (vehicle; 0.1 mL) present in the lethal dose of BPA was not lethal and had no effect on respiration, blood pressure and heart rate. The results provide evidence that the acute exposure to BPA produces lethality with a very narrow range of lethal and survival dose for iv route. Further, the lethality appears to be due to respiratory arrest and hypotension.
Aglycemia and ischemia depress monosynaptic and polysynaptic reflexes in neonatal rat spinal cord in vitro by involving different types of 5-hydroxytryptamine receptors
(2004) Shripad B. Deshpande; Archana Jha
Involvement of 5-hydroxytryptaminergic (5-HT) system for aglycemia- and ischemia-induced depression of the spinal reflexes was evaluated. The monosynaptic (MSR) and polysynaptic (PSR) reflex potentials were elicited in the ventral root by stimulating the corresponding dorsal root in an isolated spinal cord from neonatal rat. Superfusion of aglycemic (glucose-free) or ischemic (glucose- and O 2-free) solution produced a time-dependent depression of the spinal reflexes and abolished them within 35 min. The time required to produce 50% depression of the reflexes (T-50) was around 19 and 13 min for aglycemia and ischemia, respectively. Spiperone (5-HT 2A antagonist) and ketanserin, (5-HT 2A/2C antagonist) blocked the aglycemia-induced depression of the reflexes completely while ondansetron (5-HT 3 antagonist) attenuated it partially (as abolition times were around 50 min). Ischemia-induced depression was blocked up to 50 min by ketanserin or ondansetron but not by spiperone. In the presence of ketanserin or ondansetron, the reflexes were abolished by 60 min while in spiperone the reflexes were abolished by 30 min. In 5,7-dihydroxytryptamine treated rats, aglycemia depressed the reflexes by 45 min (greater than control, P < 0.05) while the time for ischemia-induced depression was not different from the control response. The results indicate that aglycemia involves mainly 5-HT 2 receptors while ischemia involves 5-HT 3 receptors. © 2004 Elsevier Ireland Ltd. All rights reserved.
Aglycemia and ischemia depress spinal synaptic transmission via inhibitory systems involving NMDA receptors
(Elsevier, 2003) Archana Jha; Shripad B. Deshpande
The effects of in vitro aglycemia (glucose-free) and ischemia (glucose-free and O2-free) were examined on the dorsal root-evoked ventral root spinal monosynaptic and polysynaptic reflexes in neonatal rat spinal cords. Aglycemia and ischemia depressed the reflexes in a time-dependent manner and abolished them by 35 min. The depression by ischemia began immediately while that by aglycemia began after 15 min. The NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), blocked the depression induced by aglycemia completely and that by ischemia partially. Strychnine (glycineA receptor antagonist) or bicuculline (GABAA receptor antagonist) blocked the aglycemia-induced depression of the reflexes. In the case of ischemia, strychnine but not bicuculline, blocked the depression partially. The results indicate that aglycemia and ischemia depress the synaptic transmission involving NMDA receptors. Aglycemia involves both γ-aminobutyric acid-ergic and glycinergic inhibitory transmission while ischemia involves other additional mechanisms. © 2003 Elsevier B.V. All rights reserved.
Ambulatory venous pressure studies and its correlation with CEAP grading of varicose veins
(Edizioni Minerva Medica, 2020) Ajay K. Khanna; Shivanshu Singh; Satyendra K. Tiwary; Soumya Khanna; Shripad B. Deshpande; Ram C. Shukla; Puneet Kumar
BACKGROUND: Venous hypertension in the lower limb is predisposing factor for the chronic venous insufficiency and resultant skin changes. In a normal limb, during ambulation, there is a fall in lower limb venous pressure as the calf muscle pump and unidirectional valvular activity propel the blood from the lower limbs to the heart. Failure of this mechanism results in ambulatory venous hypertension predisposing to chronic venous insufficiency. The current study aimed at studying the lower limb ambulatory venous pressure in varicose veins, its co-relation with clinical severity of the disease according to the clinical grading of clinical-etiological-anatomical-pathophysiological (CEAP) classification and whether these measurements can help in assessing the anatomical sites of incompetence. METHODS: A prospective study was carried out at a University Teaching Hospital in Northern India. Ambulatory venous pressure was measured in 67 limbs. Limbs were classified according to the CEAP grading. Four groups were divided as follows: group 1, CEAP-0 (7 limbs); group 2, CEAP-1, 2 (24 limbs); group 3, CEAP-3, 4 (21 limbs); and group 4, CEAP-5, 6 (15 limbs). Following the duplex scan, limbs were also grouped according to the anatomical sites of incompetence. For pressure measurement, dorsal foot vein was cannulated with a 20-gauge cannula and connected to a physiograph through a pressure transducer filled with heparinized saline. Patient performed a standard 10 tip-toe exercise and following parameters were assessed: resting pressure in the sitting and standing position, mean ambulatory venous pressure, maximum fall in pressure, percentage decrease in pressure, 50%, 75%, 90% recovery time, initial recovery rate, recovery in first 4 seconds, pressure relief index. RESULT S: Median ambulatory venous pressure showed a progressive increase from group 1 (18.0 mmHg) to group 2 (51.5 mmHg) to group 3 (69.0 mmHg) and group 4 (91.0 mmHg). Median recovery times for 50%, 75% and 90% recovery of pressure after cessation of exercise were significantly lower while the percentage recovery in first 4 seconds was significantly higher in the ulcer group. Median pressure relief index showed a significant stepwise decreasing trend from group 1 to group 4 (2790.0 mmHg-sec in group 1to 534.0 in group 2 to 534.0 in group 3 to 40.0 in group 4; P<0.001). The prevalence of ulceration increased significantly with increasing median ambulatory venous pressure and decrease in time required for 90% recovery and median pressure relief index. None of the parameters showed significant variation among all the groups divided based on anatomical sites of incompetence. CONCLUSIONS: Ambulatory venous pressure measurement correlates with the clinical grading of the CEAP classification of varicose veins. Ambulatory venous pressure measurements do not help in determining the anatomical sites of incompetence. Pressure relief index, the recovery time intervals and the mean ambulatory venous pressure are the important parameters that can help in identifying and grading the severity of the disease. © 2020 EDIZIONI MINERVA MEDICA.
Aprotinin reverses ECG abnormalities induced by mesobuthus famulus concanesis, pocock venom in adult rats
(2007) Ratna Pandey; Shripad B. Deshpande
The kinins are implicated in the pathogenesis of scorpion envenomation. Therefore, this study was carried out to examine the involvement of kinins for the ECG abnormalities induced by M. tamulus concanesis, (BT) venom in anaesthetized rats. ECG was recorded using needle electrodes with limb lead II configuration. The PR interval, QRS wave pattern, QRS duration, ST segment and heart rate were examined in saline only, venom alone, and venom after aprotinin groups. BT venom (5 mg/kg) produced heart block of varying degree and ischemia-like changes in ECG wave pattern and the animals died within 30 min after exposure to venom. In aprotinin pretreated animals, the initial ECG changes produced by venom persisted, but after 15 min the ECG pattern improved and the animals survived for the entire period of observation (120 min). The results indicate that aprotinin protected the rats against the cardiotoxicity induced by BT venom.
Art of writing a scientific paper
(2006) Shripad B. Deshpande
[No abstract available]
Augmentation of phenyldiguanide-induced bradycardia by Buthus tamulus venom in adult rats
(1996) Anil K. Tiwari; Shripad B. Deshpande
Intravenous injection of phenyldiguanide (PDG) in anaesthetized rats produced dose-dependent (1-10 μg/kg) decrease in heart rate for a period of time (time-response area). The maximum response occurred at 10 μg/kg PDG. Admmistration of B. tamulus (BT) venom as low as 20 μg/kg augmented the PDG-induced bradycardia response by 2.5 times the initial PDG (10 μg/kg) response. The maximal augmentation was observed after 60 min of venom injection. Increasing the BT venom concentration to 40 μg/kg failed to enhance the reflex response (1.7 times the initial response). The threshold concentration of BT venom was 4 μg/kg. BT venom (100 μg/kg) alone, decreased the heart rate significantly only after 90 min. Results indicate that, even the sublethal concentrations of BT venom sensitize the reflexes elicited by PDG.
B1-kinin receptors modulate Mesobuthus tamulus venom-induced vasosensory reflex responses in anesthetized rats
(Medknow Publications, 2016) Sanjeev K. Singh; Shripad B. Deshpande
Objective: Intra-arterial injection of Mesobuthus tamulus (BT) venom produces reflex vasosensory responses modulating cardiorespiratory parameters in albino rats. The present study was conducted to understand the role of kinin receptors in modulating vasosensory reflexes evoked by BT venom. Materials and Methods: In urethane-anesthetized rats, tracheostomy was performed to keep the airway patent. The femoral artery was cannulated proximally, as well as distally, to record the blood pressure (BP) and to inject the chemicals, respectively. Electrocardiographic and respiratory excursions were recorded to compute the heart rate (HR) and respiratory rate (RR). A group of animals was pretreated with saline/kinin receptor antagonists intra-arterially (B1/B2 receptor antagonists) before the injection of venom. Results: After intra-arterial injection of BT venom (1 mg/kg), there was an immediate increase in RR, which reached to 40% within 30 s, followed by a decrease of 40%. Further, there was sustained increase in RR (50%) up to 60 min. The BP started to increase at 40 s, peaking at 5 min (50%), and remained above the initial level up to 60 min. The bradycardiac response started after 5 min which peaked (50% of initial) at 25 min and remained at that level up to 60 min. In B1 receptor antagonist (des-Arg) pretreated animals, venom-induced cardiovascular responses were attenuated (by 20-25% in mean arterial pressure and HR) significantly but not in B2 receptor antagonist (Hoe-140) pretreated animals. Either of the antagonists failed to alter the RR responses. Conclusions: BT venom-induced vasosensory reflex responses modulating cardiovascular parameters are mediated via B1-kinin receptors in anesthetized rats. © 2016 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow.
Bisphenol A attenuates phenylbiguanide-induced cardio-respiratory reflexes in anaesthetized rats
(2012) Jayanti Pant; Mahendra K. Pant; Shripad B. Deshpande
Bisphenol A (BPA), a toxic chemical released from plastics, produces respiratory arrest and hypotension after a latency. The latency was similar to the reflex apnoea induced by the vagal C fibre stimulation. Therefore, the present study was undertaken to examine the effects of chronic and acute exposure to BPA on cardio-respiratory reflexes elicited by phenylbiguanide (PBG). Acute and chronic experiments were performed on adult female rats. In chronic experiments, the animals were ingested with pellets containing BPA (2. μg/kg body weight) or without BPA (time-matched control) for 30 days. Subsequently, the animals were anaesthetized and prepared for recording blood pressure, ECG and respiratory excursions. PBG was injected through jugular vein to evoke reflexes in these animals. In acute experiments, the PBG reflexes were obtained before and after injecting BPA/ethanol. Also vagal afferent activity was recorded in some rats. In time-matched control rats, PBG produced bradycardia, hypotension and tachypnoea over a period of time. The maximal changes were around 50-65%. In BPA treated group, the PBG-induced heart rate and respiratory frequency changes were attenuated significantly. Acute exposure of animals to BPA (35. mg/kg body weight) for 30. min also attenuated the PBG-induced responses significantly. The attenuation of the PBG reflex responses by BPA in acute experiments was associated with decreased vagal afferent activity. The present results indicate that BPA attenuates the protective cardio-respiratory reflexes due to decreased vagal afferent activity. © 2012 Elsevier Ireland Ltd.
Bisphenol A decreases atrial contractility involving NO-dependent G-cyclase signaling pathway
(2011) Jayanti Pant; Pratibha Ranjan; Shripad B. Deshpande
Bisphenol A (BPA) is used in manufacturing plastics. Even though BPA is reported to produce reproductive and behavioral toxicity in experimental animals, the direct effect of BPA on the cardiovascular system is not known. The present study was therefore undertaken to evaluate the effect of BPA, on spontaneously beating rat right atrial preparations. In this study, in vitro isometric contractions of right atria were recorded. Cumulative concentration-response of BPA on atrial contractions was obtained in the absence or presence of antagonists. BPA (0.1-100μ m) decreased the rate and the force of atrial contractions in a concentration-dependent manner. At 100μ m, the decreases were >90%. The BPA-induced changes were not blocked by atropine (muscarinic receptor blocker). However, pretreatment with N-ω-nitro- l-arginine methyl ester (l-NAME, a nitric oxide synthase inhibitor) or methylene blue (a guanylyl cyclase inhibitor) blocked the BPA-induced changes in rate and force. Nitroglycerine, an NO-donor, decreased the rate and force of atrial contractions. Further, the BPA-induced changes were not due to the solvent (ethanol) used to dissolve it. The present study therefore indicates that BPA decreases the atrial contractility involving NO-dependent G-cyclase signaling mechanisms. Effect of bisphenol-A (BPA), a toxic chemical present in plastics, on spontaneously beating rat right atria was examined. BPA (0.1-100 microM) reduced rate and force of atrial contractions (> 90% decrease at 100 microM). BPA-induced changes were not blocked by its solvent or by atropine. However, NOS inhibitor or G-cyclase inhibitor blocked the BPA induced changes in rate and force. Nitroglycerine (NO-donor) decreased the rate and force of atrial contractions. Therefore, BPA decreases atrial contractility by involving NO-G-cyclase signaling mechanisms. © 2011 John Wiley & Sons, Ltd.
Bisphenol A decreases the spontaneous contractions of rat uterus in vitro through a nitrergic mechanism
(De Gruyter, 2018) Hemlata Gupta; Shripad B. Deshpande
Bisphenol A (BPA), a chemical used in the manufacture of plastics, has toxic effects on various systems of the human body including the reproductive system. BPA possesses estrogenic activity and is implicated in altering oogenesis, ovulation, and fertility. In addition to ovulatory changes, uterine contractility is an important factor for fertility. However, the effects of BPA on myometrial contractions are not known. Therefore, we examined the effect of BPA on rat uterine contractions. The uterus was isolated from adult rats showing estrous phase, and spontaneous in vitro contractions were recorded (35±1 °C). The effect of cumulative concentrations of BPA was determined. Further, the involvement of nitric oxide (NO) and guanylyl cyclase (GC) for the BPA-induced changes on uterine contractility was evaluated using the NO synthase inhibitor (L-NAME) or GC inhibitor (methylene blue). BPA decreased the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner. A decrease of 50% occurred at 1 and 3 μM for amplitude and frequency, respectively. L-NAME (N-ω-nitro-l-arginine methyl ester) blocked the BPA-induced decrease in amplitude at all concentrations but antagonized the frequency only at the maximum concentration (10 μM). Methylene blue (a GC inhibitor) did not block the BPA-induced responses but for the frequency at 10 μM of BPA. The results indicate that BPA decreased the amplitude and frequency of spontaneous uterine contractions by involving the nitrergic mechanism; however, the GC mechanism is not involved in the depression. © 2018 Walter de Gruyter GmbH, Berlin/Boston.
Bisphenol A depresses compound action potential of frog sciatic nerve in vitro involving Ca2+-dependent mechanisms
(2012) Abhay K. Pandey; Shripad B. Deshpande
Bisphenol-A (BPA), a toxic chemical from polycarbonate plastics, is known for behavioural and neural abnormalities. These neuro-behavioural changes reflect the changes in neural activity. However the effect of BPA on nerve action potential is not available. Therefore, present investigation was undertaken to study the effect of BPA on compound action potential (CAP) of frog sciatic nerve. Bundle containing small group of nerve fibres in a sciatic nerve was dissected and placed in a Perspex chamber perfused with Ringer solution. Suction electrodes were applied to the cut ends of the nerve for stimulating and recording purposes. The stimulation of one end (with supramaximal strength) produced CAP in the recording electrode. BPA (1-100μM) decreased the amplitude and repolarization time of CAP in a concentration-dependent manner, without any alteration in latency, rise time and threshold. The decrease in amplitude was directly correlated with decrease in repolarization time (r=0.76). The BPA-induced decreases were absent in Ca2+-free medium or in presence of L-type Ca2+-channel antagonist (nifedipine/deltiazem). T and P type Ca2+ channel antagonist (Ni2+) failed to block the BPA-induced responses. Pre-treatment with an Erα antagonist (tamoxifen) blocked the BPA-induced decrease in CAP parameters. These observations indicate that the BPA decreased the amplitude and repolarization time of CAP involving L-type Ca2+-channel dependent mechanisms. Further involvement of Erα in the modulation of Ca2+ channels is a possibility. © 2012 Elsevier Ireland Ltd.
Bradycardia induced by Mesobuthus tamulus scorpion venom involves muscarinic receptor-G-protein-coupled cell signaling pathways
(2008) Shripad B. Deshpande; Sadhana Kanoo; Anitha B Alex
Indian red scorpion (Mesobuthus tamulus; MBT) envenomation produces various cardio-respiratory abnormalities including cardiac dysrhythmias. The underlying cell signaling pathways for the cardiac dysrhythmias produced by MBT venom are not known. The present study was therefore conducted to delineate the second messenger signaling pathways involved in MBT venom-induced atrial rhythm changes. The effects of venom and various antagonists were examined on spontaneously beating rat right atrial preparations in vitro. The MBT-venom produced an increase (35%), a decrease (45%) and again an increase (50%) in rate at 0.03, 0.3 and 3.0 μg/ml of venom, respectively. On the other hand, force of contraction exhibited a concentration-dependent rise (up to 40%) at all concentrations of venom. Pretreatment with atropine (0.3 μM) blocked the decrease in atrial rate at 0.3 μg/ml concentration of venom while no such blockade was seen in force of contraction. Submaximal concentration of ACh (0.1 nM) decreased the atrial rate by 25%. In the presence of MBT venom (0.3 μg/ml), ACh-induced fall in atrial rate was enhanced. The venom-induced fall in atrial rate and augmentation of ACh response were blocked by pertussis toxin (PTx; a Gi-inhibitor) or methylene blue (a G-cyclase inhibitor). The results indicate that the decrease in atrial rate produced by venom is mediated muscarinic by receptors via Gi-guanylyl cyclase mediated cell signaling pathways.
Buthus tamulus venom-induced vasosensory reflexes are mediated through efferent pathways in sympathetic and vagal parasympathetics
(2009) Sanjeev K. Singh; Shripad B. Deshpande
Present study was conducted to identify the efferents mediating the vasosensory reflexes evoked by intra-arterial (i.a.) injection of Mesobuthus tamulus (BT; 1 mg/kg) venom in the distal segment of femoral artery. Blood pressure (BP), electrocardiogram (ECG) and respiratory movements were recorded for 60 min after the i.a. injection of venom in urethane anaesthetised rats. Intra-arterial injection of venom produces immediate-tachypnoeic, intermediate-hypertensive and delayed-bradycardiac responses. Respiratory changes manifested as immediate increase (by 40%) in respiratory frequency (RF) followed by a decrease (by 40%) within 1 min and subsequent sustained increase (50%) up to 60 min. Increase in BP began after the respiratory changes, peaked (50%) at 5 min and remained at that level throughout. The decrease in heart rate (HR) began after 5 min, peaked (60%) at 10 min and recovered subsequently (40%) but remained below the initial level. In terazosin pretreated animals, the venom-induced cardiorespiratory changes were attenuated significantly. Whereas in vagotomized group, venom-induced respiratory changes and HR changes were blocked but not the BP changes. The findings suggest that the venom-induced vasosensory responses involve α1-adrenoceptors for BP and vagal efferents for HR changes. © 2009 Elsevier Ireland Ltd. All rights reserved.
Ca2+-free medium enhances the magnitude of slow peak in compound action potential of frog sciatic nerve in vitro
(2004) Maloy B. Mandal; Shripad B. Deshpande
The present investigation was carried out to know the effect of Ca 2+ on different peaks of compound action potential (CAP) representing the fibers having different conduction velocity. CAP was recorded from a thin bundle of nerve fibers obtained from desheathed frog sciatic nerve. Suction electrodes were used for stimulating and recording purposes. In Ca 2+-free amphibian Ringer, two distinct peaks (Peak-I and Peak-II) were observed. The threshold, conduction velocity (CV), amplitude and duration of Peak-I were 0.32±0.02 V, 56±3.0 m/sec, 2.1±0.2 mV and 0.75±0.1 ms, respectively. The Peak-II exhibited ten times greater threshold, eight times slower CV, three times lower amplitude and four times greater duration as compared to Peak-I. Addition of 2 mM Ca2+ in the bathing medium did not alter CAP parameters of Peak-I excepting 25% reduction in CV. But, in Peak-II there was 70-75% reduction in area and amplitude. The concentration-attenuation relation of Peak-II to various concentrations of Ca2+ was nonlinear and 50% depression occurred at 0.35 mM of Ca 2+. Washing with Ca2+-free solution with or without Mg2+ (2 mM)/verapamil (10 μM) could not reverse the Ca 2+-induced changes in Peak-II. Washing with Ca2+-free solution containing EDTA restored 70% of the response. The results indicate that Ca2+ differentially influence fast and slow conducting fibers as the activity of slow conducting fibers is greatly suppressed by external calcium.
Captopril augments acetylcholine-induced bronchial smooth muscle contractions in vitro via kinin-dependent mechanisms
(National Institute of Science Communication, 2016) Naman Agrawal; Aparna Akella; Shripad B. Deshpande
Angiotensin converting enzyme (ACE) inhibitors therapy is aassociated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. In vitro contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP3) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 μM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP3-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy. © 2016, National Institute of Science Communication. All rights reserved.