Acetazolamide inhibits stimulated feline liver and gallbladder bicarbonate secretion.
Bile acidification is a key factor in preventing calcium carbonate precipitation and gallstone formation. Carbonic anhydrase II (CA II), that is inhibited by acetazolamide, plays a role in regulation of the acid-base balance in many tissues. This study examines the effect of acetazolamide on secretin- and vasoactive intestinal peptide (VIP)-stimulated gallbladder mucosal bicarbonate and acid secretion. Gallbladders in anaesthetized cats were perfused with a bicarbonate buffer bubbled with CO2 in air. In 20 experiments VIP (10 microg kg(-1) h(-1)) and in 10 experiments secretin (4 microg kg(-1) h(-1)) were infused continuously intravenous (i.v.). Hepatic bile and samples from the buffer before and after perfusion of the gallbladder were collected for calculation of ion and fluid transport. During basal conditions a continuous secretion of H+ by the gallbladder mucosa was seen. Intravenous infusion of vasoactive intestinal peptide (VIP) and secretin caused a secretion of bicarbonate from the gallbladder mucosa (P < 0.01). This secretion was reduced by intraluminal (i.l.) acetazolamide (P < 0.01). Bile flow was enhanced by infusion of VIP and secretin (P < 0.01) but this stimulated outflow was not affected by i.v. acetazolamide. The presence of CA II in the gallbladder was demonstrated by immunoblotting. Biliary CA activity has an important function in the regulation of VIP- and secretin-stimulated bicarbonate secretion across the gallbladder mucosa.
Nilsson
B
B
Department of Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
Valantinas
J
J
Hedin
L
L
Friman
S
S
Svanvik
J
J
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000032:analysis; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D002256:Carbonic Anhydrases; D000086:Acetazolamide