{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:16:04Z","timestamp":1790853364755,"version":"4.1.0"},"reference-count":35,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,12,1]]},"abstract":"<jats:p>The role of intracellular guanosine 3\u2032,5\u2032-cyclic monophosphate concentration ([cGMP]<jats:sub>i<\/jats:sub>) in nitric oxide (NO)-mediated relaxations in the uterus has become controversial. We found the NO donor S-nitroso-l-cysteine (CysNO) to potently (IC<jats:sub>50<\/jats:sub>= 30 nM) inhibit spontaneous contractions in the nonpregnant human myometrium. CysNO treatment increased [cGMP]<jats:sub>i<\/jats:sub>significantly ( P &lt; 0.001), and this increase was blocked by the guanylyl cyclase inhibitors methylene blue (10 \u03bcM) or LY-83583 (1 \u03bcM); however, pretreatment with these guanylyl cyclase inhibitors failed to block CysNO-mediated relaxations. Intracellular cAMP concentrations were not altered by treatment of tissues with 10 \u03bcM CysNO. Incubation with the cGMP analogs 8-bromo-cGMP or \u03b2-phenyl-1, N<jats:sup>2<\/jats:sup>-etheno-cGMP did not significantly affect spontaneous contractility. Pretreatment of tissues with charybdotoxin [a calcium-dependent potassium channel (BK) blocker] completely reversed CysNO-induced relaxations. We conclude that NO is a potent inhibitor of spontaneous contractile activity in the nonpregnant human uterus and that, although guanylyl cyclase and BK activities are increased by NO, increases in [cGMP]<jats:sub>i<\/jats:sub>are not required for NO-induced relaxations in this tissue.<\/jats:p>","DOI":"10.1152\/ajpcell.1998.275.6.c1668","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:41:54Z","timestamp":1514137314000},"page":"C1668-C1673","source":"Crossref","is-referenced-by-count":61,"title":["Nitric oxide relaxes human myometrium by a cGMP-independent mechanism"],"prefix":"10.1152","volume":"275","author":[{"given":"Karri K.","family":"Bradley","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L. 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