{"title":"Towards an understanding of the mechanism of action of cyclic AMP and cyclic GMP in smooth muscle relaxation.","authors":"T M Lincoln, T L Cornwell","doi":"10.1159/000158852","DOIUrl":null,"url":null,"abstract":"<p><p>Cyclic GMP (cGMP) mediates the relaxing action of a variety of vasodilator drugs and endogenous vasodilator substances. Cyclic AMP (cAMP) mediates relaxation by beta-adrenergic agonists as well as other activators of adenylate cyclase. Both second messengers appear to reduce the concentration of intracellular Ca2+ in vascular smooth muscle cells, thus affecting relaxation. The presence of cGMP-dependent protein kinase in vascular smooth muscle cells is required for the reduction of Ca2+ by cAMP and cGMP, suggesting that this enzyme mediates the relaxing effects of both cyclic nucleotides. Although the specific substrate proteins for cGMP-dependent protein kinase are not well characterized in vascular smooth muscle, new evidence indicates that Ca2(+)-ATPase activation by phosphorylation of phospholamban by the kinase may underlie the mechanism of action of cyclic-nucleotide-dependent relaxation.</p>","PeriodicalId":9009,"journal":{"name":"Blood vessels","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000158852","citationCount":"206","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood vessels","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000158852","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 206
Abstract
Cyclic GMP (cGMP) mediates the relaxing action of a variety of vasodilator drugs and endogenous vasodilator substances. Cyclic AMP (cAMP) mediates relaxation by beta-adrenergic agonists as well as other activators of adenylate cyclase. Both second messengers appear to reduce the concentration of intracellular Ca2+ in vascular smooth muscle cells, thus affecting relaxation. The presence of cGMP-dependent protein kinase in vascular smooth muscle cells is required for the reduction of Ca2+ by cAMP and cGMP, suggesting that this enzyme mediates the relaxing effects of both cyclic nucleotides. Although the specific substrate proteins for cGMP-dependent protein kinase are not well characterized in vascular smooth muscle, new evidence indicates that Ca2(+)-ATPase activation by phosphorylation of phospholamban by the kinase may underlie the mechanism of action of cyclic-nucleotide-dependent relaxation.