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• W2004666564 abstract "Ryanodine-sensitive, Ca2+ release (‘Ca2+ sparks’) from the sarcoplasmic reticulum (SR) can activate plasmalemmal Ca2+-activated K+ channels (KCa) to cause membrane hyperpolarization and smooth muscle relaxation. Since cyclic guanosine monophosphate (cyclic GMP) can modulate Ca2+ spark activity, the aim of the present study was to determine if Ca2+ spark-like events are involved in NO-dependent, NANC relaxations to electrical field stimulation (EFS) of mouse, longitudinal smooth muscle of the gastric fundus in isolated strips contracted to ∼40% of their maximum contraction. NANC relaxations to EFS were almost abolished by both the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG; 100 μM) and the guanylate cyclase inhibitor, 1-H-oxodiazol-[1,2,4]-[4,3-α] quinoxaline-1-one (ODQ; 10 μM). Also, ODQ abolished relaxations to the NO donor, sodium nitroprusside (SNP; 1 nM–30 μM). NANC relaxations and SNP-evoked relaxations were both partly ryanodine (10 μM)- and nifedipine (0.3 μM)-sensitive, but in each case, the inhibitory effects of ryanodine and nifedipine were additive. Apamin (1 μM), charybdotoxin (0.1 μM), iberiotoxin (0.1 μM), tetraethylammonium (TEA; 1 mM), glibenclamide (10 μM) and 4-aminopyridine (1 mM) had no effect on either NANC- or SNP-evoked relaxations, the latter of which were also unaffected by high extracellular K+ (68 mM). Caffeine (0.1–1 mM) caused concentration-dependent relaxations of gastric fundus which were inhibited by ryanodine but unaffected by L-NOARG. Relaxation to ATP (30 μM) was abolished by nifedipine, partly inhibited by apamin and ryanodine, but was unaffected by L-NOARG. In conclusion, the results of the present study show that nitrergic relaxations in the mouse longitudinal gastric fundus occur via a cyclic GMP-activated ryanodine-sensitive mechanism, which does not appear to involve activation of K+ channels. British Journal of Pharmacology (2000) 129, 1315–1322; doi:10.1038/sj.bjp.0703174" @default.
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• W2004666564 date "2000-04-01" @default.
• W2004666564 modified "2023-09-26" @default.
• W2004666564 title "Nitrergic relaxation of the mouse gastric fundus is mediated by cyclic GMP-dependent and ryanodine-sensitive mechanisms" @default.
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• W2004666564 doi "https://doi.org/10.1038/sj.bjp.0703174" @default.
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