Both soluble guanylate cyclase and particulate guanylate cyclase regulate myometrial contractility

Syal, Ashu S.; Vedernikov, Yuri P.; Chwalisż, Kristof; Saade, George R.; Garfield, Robert E.

doi:10.1016/s0002-9378(98)70259-5

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…Inhibitory effect on uterine contractile activity of NO is accentuated during pregnancy and decreased toward term (2,4,6,16). DEA / NO spontaneously releasing NO with an estimated half-life of about 2.1 min in solution with pH 7.4 at 37°C (22) relaxed vascular smooth muscle (8) and inhibited spontaneous contractions of myometrium during pregnancy, but not at term (2,4,23). The greater inhibitory effect of DEA / NO on spontaneous uterine contractions in pregnant uterine horn is associated with greater expression of iNOS mRNA in this experiments.…”

Section: Discussionmentioning

confidence: 99%

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

et al. 2004

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Abstract. Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine / nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident.

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Section: Discussionmentioning

confidence: 99%

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

et al. 2004

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“…The membrane-bound form of guanylate cyclase (GC m ) also regulates myometrial cGMP production and contractility (22). CRH acutely increased basal and ANP-stimulated GC m activity, an effect that appeared to be independent of NOS activity.…”

Section: Discussionmentioning

confidence: 99%

“…Myometrial cGMP production can be also regulated by atrial natriuretic peptide (ANP), which activates the membrane-bound guanylate cyclase (GC m ) (22), the cell surface receptor for ANP (23). ANP receptors are widespread within myometrium and other feto-maternal tissues (24) where they possibly mediate ANP's vasodilatory actions on uteroplacental vessels (25).…”

mentioning

confidence: 99%

Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells

Aggelidou

Hillhouse

Grammatopoulos

2002

Proc. Natl. Acad. Sci. U.S.A.

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The biological actions of corticotropin-releasing hormone (CRH) in the human myometrium during pregnancy and labor are unknown. We hypothesized that CRH may modulate the nitric oxide system, and influence myometrial relaxation͞contractility. Incubation of myometrial cells with CRH, but not urocortin II or urocortin III, for 8 -16 h significantly induced mRNA and protein expression of endothelial and brain but not inducible nitric oxide synthase (NOS) isoforms. This action resulted in increased activity of soluble guanylate cyclase (GC s), demonstrated by the enhanced cGMP-producing capacity of the NO donor, sodium nitroprusside. CRH also caused acute activation of the membrane-bound GC, shown by increased basal or atrial natriuretic peptide (ANP)-stimulated cGMP production. These effects appeared to be mediated via the R1 receptors because the CRH receptor antagonists, astressin and antalarmin but not anti-sauvagine 30, could block them. The acute effects of CRH were significantly reduced by inhibition of protein kinase A (PKA) activity, suggesting it is partially PKA dependant. Activation of protein kinase C (PKC) resulted in significant inhibition of both ANP-and CRH-stimulated cGMP production, suggesting a direct effect of PKC on membrane-bound GC. In conclusion, CRH appears to have a dual effect on myometrial NOS͞GC pathway, a short term effect predominantly mediated by PKA, and a long-term effect increasing constitutive NOS expression, mediated by a PKA-independent mechanism. This mechanism could potentially be active during human pregnancy, and, because cGMP stimulates myometrial relaxation, these findings further suggest that during pregnancy CRH primarily activates intracellular signals that contribute to the maintenance of myometrial quiescence.

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“…Further, conflicting evidence has emerged regarding the ability of cGMP to relax smooth muscle. Based on a decreased response to cGMP analogs, it was suggested that certain types of smooth muscles are "sensitive," whereas others are "nonsensitive" to cGMP-induced relaxation (Hennan and Diamond, 1998;Syal et al, 1998;Word and Cornwell, 1998).…”

Section: Mechanism Of Cgmp-mediated Smoothmentioning

confidence: 99%

Molecular mechanism of cGMP-mediated smooth muscle relaxation

et al. 2000

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Contraction and relaxation of smooth muscle is a tightly regulated process involving numerous endogenous substances and their intracellular second messengers. We examine the key role of cyclic guanosine monophosphate (cGMP) in mediating smooth muscle relaxation. We briefly review the current art regarding cGMP generation and degradation, while focusing on the recent identification of the molecular mechanisms underlying cGMP-mediated smooth muscle relaxation. cGMP-induced SM relaxation is mediated mainly by cGMP-dependent protein kinase activation. It involves several molecular events culminating in a reduction in intracellular Ca(2+) concentration and a decrease in the sensitivity of the contractile system to Ca(2+). We propose that the cGMP-induced decrease in Ca(2+) sensitivity is a strategic way to achieve "active relaxation" of the smooth muscle. In summary, we present compelling evidence supporting a key role for cGMP as a mediator of smooth muscle relaxation in physiological and pharmacological settings.

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Both soluble guanylate cyclase and particulate guanylate cyclase regulate myometrial contractility

Cited by 8 publications

References 21 publications

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells

Molecular mechanism of cGMP-mediated smooth muscle relaxation

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