Selective blockage of cell membrane K conductance by an antisecretory agent in guinea-pig gallbladder epithelium.
Loperamide inhibits PGE1-induced electrogenic HCO3 secretion in guinea-pig gallbladder. Underlying changes in epithelial cell membrane properties were investigated using intracellular microelectrode techniques in vitro. In the absence of PGE1, mucosal loperamide (10(-4) mol/l) reversibly depolarized both cell membranes by approximately 6 mV. The apparent ratio of membrane resistances (Ra/Rb) remained unchanged and so did voltage responses to luminal Cl removal and Na reduction. The depolarizing response to elevation of luminal K concentration from 5 to 76 mmol/l was decreased from 13 to 8 mV. In the presence of 1 PGE1, the apical membrane is mainly permeable to Cl and HCO3. Under these conditions, loperamide reduced membrane potentials by approximately 10 mV, Ra/Rb remaining constant at approximately 0.4. Effects on voltage responses to changes in luminal Na or K concentration were unchanged. Responses to luminal Cl removal (transient depolarization) were greatly enhanced (from 22 to 42 mV) as predictable from the fall in K permeability that hinders Cl efflux from cell into lumen. Less marked but significant effects were obtained with 10(-5) mol/l (mucosal side) and serosal loperamide (10(-4) mol/l). We suggest that loperamide inhibits electrogenic HCO3 secretion by reducing apical membrane K permeability. The resulting depolarization diminishes the driving force for conductive anion efflux from cell into lumen. This conclusion is supported by the ability of luminal K elevation to mimick loperamide inhibition of the secretory flux of HCO3 (pH-stat experiments).
Abteilung Pharmakologie der Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, Federal Republic of Germany.
F
F
Wehner
J M
JM
Winterhager
K U
KU
Petersen
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D008139:Loperamide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000493:pharmacokinetics*
D001639:Bicarbonates; D010880:Piperidines; D008139:Loperamide; D011188:Potassium