Regulation of ion transport in porcine gallbladder: effects of VIP and norepinephrine

Abstract

The objective of this study was to investigate the effects of vasoactive intestinal peptide (VIP) and norepinephrine (NE) on Na and Cl transport across the isolated porcine gallbladder. Serosal addition of either VIP or secretin increased the short-circuit current (Isc). The half-maximal effect for VIP was 84.3 nM. The effect of VIP was mimicked by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). Replacement of Cl with gluconate nearly abolished the effect of 8-BrcAMP on Isc, whereas HCO3 replacement with N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid buffer had no effect. Transepithelial flux measurements indicated that 8-BrcAMP stimulates net Cl secretion and inhibits Na absorption. Norepinephrine inhibits VIP-stimulated changes in Isc as well as the basal Isc. NE does not, however, reverse the effects of 8-BrcAMP on Isc. The effects of NE are antagonized by yohimbine (alpha 2-adrenergic receptor antagonist) but not prazosin (an alpha 1-adrenergic receptor antagonist). VIP causes a 2.5-fold increase in cAMP content in the gallbladder epithelium. This increase is blocked by NE. Serosal tetrodotoxin did not inhibit the peptide effects, indicating that VIP receptors are localized on the epithelium. Depolarization of submucosal nerves with veratrine inhibited the basal Isc and was reversible with yohimbine. This result indicated that sympathetic nerve pathways regulate Na and Cl absorption in vitro.