Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways

Summary

In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO ^sup−_inf3 secretion into an electrogenic process. The effects of blood side Ba²⁺ (5 mmol/l) on HCO ^sup−_inf3 tranport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO ^sup−_inf3 and transepithelial electrical characteristics.

Serosal, not mucosal addition of Ba²⁺ elevated short-circuit current (I_sc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO ^sup−_inf3 flux while leaving the secretory flux unchanged. The I_sc effect of Ba²⁺ was inhibited or prevented by tetrodotoxin; D- and Lrpropranolol; the Cl⁻ channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca²⁺ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO ^sup−_inf3 -free solutions. Thus Ba²⁺ appeared to release a neurotransmitter that gives rise to CAMP synthesis sufficcient to turn part of electroneutral HCO ^sup−_inf3 secretion electrogenic.

In a search for the involved signalling pathways, the H₁-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the I_sc effect of Ba²⁺. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimick the action of Ba²⁺ and I_sc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 × 10⁻⁷ mol/l) completely transformed HCO ^sup−_inf3 secretion into an electrogenic process. The VIP receptor antagonist (4Cl-dPhe⁶, Leu¹⁷)VIP, delayed and reduced the I_sc responses to Ba²⁺ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba²⁺ is likely to act by releasing VIP from neural terminals.