S-nitrosocysteine, but not sodium nitroprusside, produces apamin-sensitive hyperpolarization in rat gastric fundus.
1. To investigate the pharmacological properties of the membrane hyperpolarization induced by electrical field stimulation (EFS), sodium nitroprusside (SNP) and S-nitrosocysteine (NO-Cys) in circular smooth muscle cells of the rat gastric fundus (forestomach), the effects of various potassium channel blockers on these hyperpolarizations were investigated. 2. EFS (50 microseconds, 20 Hz, 3 pulses, 10-50 V) produced inhibitory junction potentials (i.j.ps), in the presence of atropine (1 microM) and guanethidine (1 microM). NO-Cys and SNP produced hyperpolarization of the membrane in the rat gastric fundus. L-NG-nitroarginine (L-NNA) inhibited the i.j.ps, but not the hyperpolarization induced by NO-Cys and SNP. This inhibitory action of L-NNA on the i.j.ps was partly reversed by subsequent application of L-arginine (1 mM) but not by D-arginine. 3. Oxyhaemoglobin (Oxy-Hb; 5 microM) inhibited these hyperpolarizations, although a higher concentration of Oxy-Hb was required to inhibit the SNP-induced hyperpolarization. Hydroquinone (50 microM) inhibited only the hyperpolarization induced by NO-Cys. 4. Apamin (1 microM) partly inhibited i.j.ps and NO-Cys-induced hyperpolarization, but not the SNP-induced hyperpolarization. Tetraethylammonium (TEA; 1 mM), 4-aminopyridine (4-AP; 1 mM) or glibenclamide (1 microM) did not affect hyperpolarization induced by NO-Cys and SNP. 5. 8-Bromo cyclic guanosine 3':5'-monophosphate (1 mM) also produced hyperpolarization. Apamin (1 microM), TEA (1 mM) and glibenclamide (5 microM) all failed to inhibit this hyperpolarization. 6. These results indicate that NO-Cys and EFS hyperpolarize the membrane by activating apaminsensitive and TEA-resistant K+ channels and favour the hypothesis that a NO-liberating substance may act as a neurotransmitter in non-adrenergic, non-cholinergic (NANC) neurones in the rat forestomach.Our results also suggest that increase in cyclic GMP may cause apamin-resistant hyperpolarization but the apamin-sensitive hyperpolarization is mediated by another mechanism.
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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Kitamura
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Lian
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Carl
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Kuriyama
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005748:Gastric Fundus / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000294:innervation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols
D010108:Oxyhemoglobins; D026403:S-Nitrosothiols; D009599:Nitroprusside; D001030:Apamin; D009569:Nitric Oxide; D003994:Bucladesine; C021315:S-nitrosocysteine; D003545:Cysteine