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Nitric oxide relaxes human myometrium by a cGMP-independent mechanism

Nitric oxide relaxes human myometrium by a cGMP-independent mechanism Abstract The role of intracellular guanosine 3′,5′-cyclic monophosphate concentration (cGMP i ) 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 50 = 30 nM) inhibit spontaneous contractions in the nonpregnant human myometrium. CysNO treatment increased cGMP i significantly ( P < 0.001), and this increase was blocked by the guanylyl cyclase inhibitors methylene blue (10 μM) or LY-83583 (1 μM); 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 μM CysNO. Incubation with the cGMP analogs 8-bromo-cGMP or β-phenyl-1, N 2 -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 i are not required for NO-induced relaxations in this tissue. guanosine 3′,5′-cyclic monophosphate contraction Footnotes Address for reprint requests: M. E. Bradley, Dept. of Pharmacology, Creighton University, 2500 California Plaza, Omaha, NE 68178. This work was supported by National Institute of Child Health and Human Development Grants HD-33430 (M. E. Bradley) and HD-26227 (I. L. O. Buxton). Current address of K. K. Bradley: Dept. of Pharmacology, Creighton University, 2500 California Plaza, Omaha, NE 68178. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

Nitric oxide relaxes human myometrium by a cGMP-independent mechanism

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The American Physiological Society
Copyright
Copyright © 2010 the American Physiological Society
ISSN
0363-6143
eISSN
1522-1563
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Abstract

Abstract The role of intracellular guanosine 3′,5′-cyclic monophosphate concentration (cGMP i ) 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 50 = 30 nM) inhibit spontaneous contractions in the nonpregnant human myometrium. CysNO treatment increased cGMP i significantly ( P < 0.001), and this increase was blocked by the guanylyl cyclase inhibitors methylene blue (10 μM) or LY-83583 (1 μM); 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 μM CysNO. Incubation with the cGMP analogs 8-bromo-cGMP or β-phenyl-1, N 2 -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 i are not required for NO-induced relaxations in this tissue. guanosine 3′,5′-cyclic monophosphate contraction Footnotes Address for reprint requests: M. E. Bradley, Dept. of Pharmacology, Creighton University, 2500 California Plaza, Omaha, NE 68178. This work was supported by National Institute of Child Health and Human Development Grants HD-33430 (M. E. Bradley) and HD-26227 (I. L. O. Buxton). Current address of K. K. Bradley: Dept. of Pharmacology, Creighton University, 2500 California Plaza, Omaha, NE 68178. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1998 the American Physiological Society

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Dec 1, 1998

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