Electrogenic and electroneutral HCO3-secretion by guinea pig gallbladder epithelium: discriminatory abilities of Cl- channel blockers.
The specificity of Cl- channel blockers (including 5-nitro-2-(3-phenylpropylamino-)benzoic acid (NPPB), diphenylamine-carboxylic acid and 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid (MPTC)) was studied in guinea pig gallbladder. This epithelium performs electroneutral HCO3- secretion, due to cell-to-lumen exit by Cl-/HCO3- exchange. At high intracellular cyclic AMP levels [produced by prostaglandin E1, (PGE1)], secretion turns electrogenic, secondary to induction of apical membrane Cl- and HCO3- conductances. Part of HCO3- secretion remains Cl(-)-dependent. Microelectrode, voltage-clamp and pH-stat techniques were used to determine membrane potentials, short-circuit current (Isc) and secretory HCO3- fluxes. With one exception, effective agents (concentration range 10(-5)-10(-4) M, luminal bath) including NPPB and diphenylamine-carboxylic acid inhibited secretory HCO3- fluxes in the presence and absence of PGE1 as well as PGE1-induced Isc. At 10(-4) M, inhibition of Isc was not attenuated by Cl- removal; however, NPPB effects were less at concentrations < 10(-4) M. MPTC (3 x 10(-5)-3 x 10(-4) M) only partly inhibited PGE1-induced Isc, was almost ineffective in Cl(-)-free solutions, and did not affect secretory HCO3- flux under any condition. Effects of NPPB and MPTC were distinct from those of the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. This agent (10(-7)-10(-5) M), failed to discriminate between Cl(-)-dependent and -independent Isc. In control tissues, 10(-5) M carboyl cyanide p-trifluoromethoxy-phenylhydrazone practically abolished membrane potentials, whereas 10(-4) M NPPB produced no change.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
K U
KU
Institut für Pharmakologie und Toxikologie, Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule, Aachen, Federal Republic of Germany.
Cormann
P
P
Macherey
H J
HJ
Sprakties
G
G
Winterhager
J M
JM
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000502:physiology; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005704:Gallbladder / Q000378:metabolism* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009579:Nitrobenzoates / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D001639:Bicarbonates; D002352:Carrier Proteins; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D008565:Membrane Proteins; D009579:Nitrobenzoates; D013876:Thiophenes; D062367:ortho-Aminobenzoates; C082215:4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C001209:fenamic acid; D000527:Alprostadil