| 8392563 |
Petersen KU, Cormann P, Macherey HJ, Sprakties G, Winterhager JM: Electrogenic and electroneutral HCO3-secretion by guinea pig gallbladder epithelium: discriminatory abilities of Cl- channel blockers. J Pharmacol Exp Ther. 1993 Jul;266(1):65-73.
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) |
38(0,1,2,3) |