In-vitro contractility of normal human vermiform appendix involves 5-hydroxytryptamine (5-HT3) pathways in addition to muscarinic transmission

Abstract

Appendicitis is a cause of health concern in all age and sex worldwide. Alteration in appendicular peristalsis/contractility has been implicated as a precipitating factor in appendicitis. But, the neurotransmitters involved in the contractility of normal human vermiform appendix are not well understood. The present study was undertaken to investigate the neurotransmitter mediated pathways involved in mediating the contractility of longitudinal muscles of normal human vermiform appendix. Longitudinal muscle strips of human vermiform appendix were mounted in Dale's organ bath. In vitro contractility to agonist was recorded using Statham's isometric force displacement transducer. Experiments were performed to determine the dose-response of agonists (acetylcholine/5-HT/ histamine) and the dose that produced maximum contractions. In a separate set of experiments, the effect of antagonists (like atropine, ondansetron and chlorpheniramine maleate) on the agonist-induced contractions was evaluated. Acetylcholine (ACh) and 5-HT produced dose-dependent increase in contractions. ACh produced maximum contractions at 10 μM and it was partially (70%) but significantly blocked (p < 0.05) by atropine (100 μM) pretreatment. 5-HT produced maximum contractions at 1 μM and it was blocked (p < 0.05) by 5-HT3 antagonist, ondansetron (10μM). The contractions produced by histamine were small, hence effect of histamine antagonist on histamine induced contractions were not analyzed. Thus, the present study suggests the involvement of 5-HT3 pathway in addition to cholinergic-muscarinic transmission in mediating the contractility of normal human appendix. Histamine plays a minor role in overall contractility of normal appendix.