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) 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 solutions, NPPB (10 microM) inhibited calcium (Ca)-sensitive chloride currents (ICl(Ca)) evoked by caffeine (10 mM) and by noradrenaline (10 microM) by 58% and 96%, respectively. 3. At a holding potential of -2 mV in potassium (K)-containing solutions, NPPB (10 microM) inhibited charybdotoxin-sensitive K-currents (IBK(Ca)) induced by noradrenaline (10 microM) and acetylcholine (10 microM) by approximately 90%. In contrast, IBK(Ca) induced by caffeine (10 mM) was unaffected in the presence of NPPB (10 microM). Conversely, IBK(Ca) elicited by caffeine (2 mM) was reduced by approximately 50% whereas IBK(Ca) evoked by noradrenaline (50 microM) was not significantly inhibited by NPPB. 4. In K-containing solutions, NPPB (10 microM) abolished spontaneous transient outward currents (STOCs) and induced a slowly-developing outward K-current. Bath application of glibenclamide (10 microM) 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 microM) inhibited voltage-sensitive Ca-currents. 6. In Ca-free, K-containing solutions and in the presence of glibenclamide (5 microM), IBK(Ca) induced by 20 microM NS1619 was enhanced by NPPB (10 microM). 7. It is concluded that NPPB inhibits agonist-induced ICl(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 ICl(Ca) and IBK(Ca) and on STOCs probably involves an inhibitory action on intracellular Ca-stores.
Kirkup
A J
AJ
School of Biological Sciences, University of Manchester.
Edwards
G
G
Weston
A H
AH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009579:Nitrobenzoates / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley
D001562:Benzimidazoles; D018118:Chloride Channels; D009579:Nitrobenzoates; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D018999:Charybdotoxin; C086491:NS 1619; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D002110:Caffeine; D000109:Acetylcholine; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine