Endothelin-3 induces both human and opossum gallbladder contraction mediated mainly by endothelin-B receptor subtype in vitro.

Abstract

Endothelins are produced by gallbladder epithelial cells, suggesting a role in the regulation of gallbladder function. To characterize the effect of endothelin-3 (ET-3) on human and Australian possum gallbladder contractility and identify the receptor(s) involved. Human and possum gallbladder muscle strips were exposed to cumulative concentrations of ET-3 (10 pmol/L-100 nmol/L). Strips were pretreated with either tetrodotoxin (TTX) (1 micro mol/L), the selective ET receptor antagonists BQ-123 (ET(A)), BQ-788 (ET(B)), alone or together, or the mixed ET antagonist tezosentan (all 1 micro mol/L). Maximal changes in tone were measured and expressed as percentage of carbachol (100 micro mol/L)-induced tone. ANOVA was used for statistical analysis. Endothelin-3 induced a concentration-dependent increase in tone in both human and pos-sum strips (P < 0.05) and at 100 nmol/L represented 44.2 +/- 4.5% and 40.3 +/- 4.6% of carbachol-induced tone, respectively. The effect on human strips was TTX insensitive, whereas the possum concentration-response curve was shifted to the right. Individually, BQ-123 and BQ-788 shifted the human concentration-response curve to the right, but a greater inhibition by BQ-788 was achieved in the possum (P < 0.05). However, BQ-123 plus BQ-788 further reduced the ET-3 effect (P < 0.001) to a level comparable to that observed in the presence of tezosentan in both human and possum strips. Endothelin-3 produces potent gallbladder contraction in vitro, acting mainly via ET(B) receptors and also interacting with ET(A)receptors. The receptors are located on the smooth muscle, but in possum gallbladder, neural receptors may also be involved. These findings suggest that ET-3 may regulate motility of possum and human gallbladder.