title: Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways.
abstract: In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO3- secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO3- transport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO3- and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO3- flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and L-propranolol; the Cl- channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)ocytl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO3(-)-free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to cAMP synthesis sufficient to turn part of electroneutral HCO3- 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 Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimic the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 x 10(-7) mol/l) completely transformed HCO3- secretion into an electrogenic process. The VIP receptor antagonist (4Cl-DPhe6, Leu17) VIP, delayed and reduced the Isc 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.
authors.affiliation: Institut für Pharmakologie und Toxikologie der Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.
authors.forename: K U
authors.initials: KU
authors.lastname: Petersen
authors.forename: R
authors.initials: R
authors.lastname: Goergen
authors.forename: F
authors.initials: F
authors.lastname: Höfken
authors.forename: H J
authors.initials: HJ
authors.lastname: Macherey
authors.forename: G
authors.initials: G
authors.lastname: Sprakties
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D004558:Electric Stimulation; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
chemical_list: D001639:Bicarbonates; D006634:Histamine H1 Antagonists; D015221:Potassium Channels; D001464:Barium; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D000527:Alprostadil