Agonist-specific compartmentation of cGMP action in myometrium.

The Journal of Pharmacology and Experimental Therapeutics
I L BuxtonS Tichenor

Abstract

Nitric oxide relaxes myometrium in a cGMP-independent manner. Although cGMP activates its cognate kinase, this is not required for the inhibitory effect of nitric oxide. Thus, nitric oxide-mediated cGMP elevation does not enjoy the same set of substrates as it does in other smooth muscles. To further understand the regulation of relaxation of uterine muscle by cGMP, we have studied the actions of peptide-mediated cGMP action in guinea pig myometrium. We used both functional and biochemical studies of the action of the particulate guanylyl cyclase activator uroguanylin and its receptor, particulate guanylyl cyclase type C, to address the relationship between cGMP elevation acting in the membrane signaling domain to that of the nonmembrane region of the cell. Uroguanylin relaxed oxytocin-induced contractions in a dose-dependent fashion only in pregnant myometrium. Both relaxation and cGMP accumulation after uroguanylin stimulation were blocked by the putative particulate guanylyl cyclase type C inhibitors 2-chloro-ATP and isatin (1H-indole-2,3-dione), but not by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-A]quinoxalin-1-one (ODQ). Uroguanylin stimulated cGMP accumulation only in the pregnant myometrium. Caveol...Continue Reading

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Citations

Jun 7, 2011·Acta Pharmacologica Sinica·Iain L O BuxtonCraig Ulrich
Apr 11, 2017·Critical Reviews in Biochemistry and Molecular Biology·Scott D Barnett, Iain L O Buxton
Nov 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vibhuti VyasK Joseph Hurt
Jan 18, 2013·American Journal of Physiology. Cell Physiology·Trent ButlerEng-Cheng Chan
Aug 21, 2013·American Journal of Physiology. Cell Physiology·Craig UlrichIain L O Buxton
Apr 17, 2021·Biochemical Society Transactions·Jonathan K H LiMark R Johnson

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