Investigation of the effects of 5‐nitro‐2‐(3‐phenylpropylamino)‐ benzoic acid (NPPB) on membrane currents in rat portal vein

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Abstract
1 The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) were investigated on evoked and spontaneous currents in freshly-isolated cells from the rat portal vein by use of conventional whole-cell recording and perforated-patch techniques. 2 At a holding potential of −60 mV in potassium-free, caesium-containing solution, NPPB (10 μm) inhibited calcium (Ca)-sensitive chloride currents (Ici(ca)) evoked by caffeine (10 mM) and by noradrenaline (10 μm) by 58% and 96%, respectively. 3 At a holding potential of −2 mV in potassium (K)-containing solutions, NPPB (10 μm) inhibited charybdotoxin-sensitive K-currents (IBK(ca)) induced by noradrenaline (10 μm) and acetylcholine (10 μm) by approximately 90%. In contrast, IBK(ca)) induced by caffeine (10 mM) was unaffected in the presence of NPPB (10 μm). Conversely, IBK(ca) elicited by caffeine (2 mM) was reduced by approximately 50% whereas IBK(ca) evoked by noradrenaline (50 μm) was not significantly inhibited by NPPB. 4 In K-containing solutions, NPPB (10 μm) abolished spontaneous transient outward currents (STOCs) and induced a slowly-developing outward K-current. Bath application of glibenclamide (10 μm) abolished the outward current but did not antagonize the inhibitory effects of NPPB on STOCs or on IBK(Ca) evoked by noradrenaline. 5 In caesium-containing solutions, NPPB (30 μm) inhibited voltage-sensitive Ca-currents. 6 In Ca-free, K-containing solutions and in the presence of glibenclamide (5 μm), IBK(ca) induced by 20 μm NS1619 was enhanced by NPPB (10 μm). 7 It is concluded that NPPB inhibits agonist-induced ICi(ca) in rat portal vein smooth muscle. However, this agent also inhibits agonist-evoked IBK(ca) and STOCs. Moreover, NPPB inhibits voltage-sensitive Ca-currents and stimulates a glibenclamide-sensitive K-current and IBK(Ca). The effects of this agent on evoked ICi(Ca) and IBK(Ca) and on STOCs probably involves an inhibitory action on intracellular Ca-stores.