A MAXI CL- CHANNEL COUPLED TO ENDOTHELIN-B RECEPTORS IN THE BASOLATERAL MEMBRANE OF GUINEA-PIG PARIETAL-CELLS

1. To study endothelin (ET) receptors in guinea-pig stomach, ET-bindin g assays and in vitro autoradiography were performed on fundic cell su spensions and on sections of the fundus, respectively. ET(A) and ET(B) receptor subtypes were found to coexist in the parietal cells. 2. End othelin 1 (ET-1) added to the (basolateral) bathing solution was found to activate noisy whole-cell Cl- currents within about 1 min in both single, isolated parietal cells and those within gastric glands obtain ed from the fundus. 3. ET-1-induced Cl- currents were rapidly blocked by a Cl- channel blocker (NPPB) added to the (basolateral) bathing sol ution in a concentration-dependent manner with a half-maximum inhibiti on concentration of 33 mu M. 4. The anion selectivity sequence of the ET-1-induced conductance was I->Br->Cl->F-, corresponding to Eisenman' s sequence I. 5. Changes in extracellular pH between 5 and 8 did not a ffect the ET-1-induced activation of Cl- currents. 6. Similar activati ng effects were also observed with ET-3 and a specific ET(B) receptor agonist (IRL162O). An ET(B) receptor antagonist (IRL1720) prevented th e ET-1 effect, whereas an ET(A)-selective antagonist (FR139317 or BQ12 3) failed to antagonize the ET-1 effect. 7. In the whole-cell mode, un itary Cl- channel events could be observed in association with ET-1-ac tivated macroscopic currents. The single-channel conductances were aro und 200 and 350 pS at negative and positive membrane potentials, respe ctively. 8. It is concluded that gastric parietal cells of guinea-pig possess pH-insensitive 'maxi' Cl- channels coupled to ET(B) receptors in the basolateral membrane.