INVESTIGATION OF THE EFFECTS OF 5-NITRO-2-(3-PHENYLPROPYLAMINO)-BENZOIC ACID (NPPB) ON MEMBRANE CURRENTS IN RAT PORTAL-VEIN

1 The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) w ere investigated on evoked and spontaneous currents in freshly-isolate d cells from the rat portal vein by use of conventional whole-cell rec ording and perforated-patch techniques. 2 At a holding potential of -6 0 mV in potassium-free, caesium-containing solutions. NPPB (10 mu M) i nhibited calcium (Ca)-sensitive chloride currents (I-Cl(Ca)) evoked by caffeine (10 mM) and by noradrenaline (10 mu M) by 58% and 96%, respe ctively. 3 At a holding potential of -2 mV in potassium (K)-containing solutions, NPPB (10 mu M) inhibited charybdotoxin-sensitive K-current s (I-BK(Ca)) induced by noradrenaline (10 mu M) and acetylcholine (10 mu M) by approximately 90%. In contrast, I-BK(Ca) induced by caffeine (10 mM) was unaffected in the presence of NPPB (10 mu M). Conversely, I-BK(Ca) elicited by caffeine (2 mM) was reduced by approximately 50% whereas I-BK(Ca) evoked by noradrenaline (50 mu M) was not significant ly inhibited by NPPB. 4 In K-containing solutions, NPPB (10 mu M) abol ished spontaneous transient outward currents (STOCs) and induced a slo wly-developing outward K-current. Bath application of glibenclamide (1 0 mu M) abolished the outward current but did not antagonize the inhib itory effects of NPPB on STOCs or on I-BK(Ca) evoked by noradrenaline. 5 In caesium-containing solutions, NPPB (30 mu M) inhibited voltage-s ensitive Ca-currents. 6 In Ca-free, K-containing solutions and in the presence of glibenclamide (5 mu M), I-BK(Ca) induced by 20 mu M NS1619 was enhanced by NPPB (10 mu M). 7 It is concluded that NPPB inhibits agonist-induced I-Cl(Ca) in rat portal vein smooth muscle. However, th is agent also inhibits agonist-evoked I-BK(Ca) and STOCs. Moreover, NP PB inhibits voltage-sensitive Ca-currents and stimulates a glibenclami de-sensitive K-current and I-BK(Ca) The effects of this agent on evoke d I-Cl(Ca) and I-BK(Ca) and on STOCs probably involves an inhibitory a ction on intracellular Ca-stores.