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pubmed-article:15149737pubmed:abstractTextActivation of the intracellular cAMP-signaling pathway by either forskolin or the cAMP-mimetic dibutyryl cAMP significantly increased transcript levels of NPR-C in primary cultures of human aortic smooth muscle cells. The time course of the increase was rapid, with significant differences from control occurring within 3 h of treatment and reaching approximately 6 times control value after 24 h of exposure to 10 microM forskolin. Expression levels of the natriuretic peptide receptor B (NPR-B), but not the natriruetic peptide receptor A (NPR-A) were also increased by forskolin, rising to a level of approximately 2 times control at 96 h. NPR-B transcript levels in the presence of dibutyryl cAMP were unaltered by the protein kinase A (PKA) inhibitor KT-5720, suggesting a PKA-independent pathway to NPR-B up-regulation. In contrast, KT-5720 reduced NPR-C transcript to a lower level that was not significantly different from control. Partial re-differentiation of AOSMC by culture in growth factor-reduced matrix (Matrigel) did not significantly change NPR-C transcript levels compared with cells grown on plastic, and the dibutyryl cAMP-induced increase in NPR-C (approximately eight-nine-fold control value) was retained. The dibutyryl cAMP/forskolin effect on NPR-C transcript was not reproduced by the beta2-selective adrenergic agonist isoproterenol (10 microM), but was replicated by incubation with the phosphodiesterase inhibitor isobutylmethylxanthine (0.5 mM). Up-regulated NPR-B and NPR-C transcript levels were reflected, respectively, in a two-fold increase in CNP-stimulated cGMP and an increase in 125I-ANF binding competed by the NPR-C-specific natriuretic peptide, C-ANF(4-23) following a 4-day treatment with 0.125 mM dbcAMP. The present data suggest that elevation of cAMP in human vascular smooth muscle may potentiate the vasoactive effects of natriuretic peptides acting through the NPR-B and NPR-C receptors.lld:pubmed
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pubmed-article:15149737pubmed:copyrightInfoCopyright 2004 Elsevier Ireland Ltd.lld:pubmed
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pubmed-article:15149737pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:15149737pubmed:articleTitleCyclic adenosine monophosphate (cAMP) increases natriuretic peptide receptor C (NPR-C) expression in human aortic smooth muscle cells.lld:pubmed
pubmed-article:15149737pubmed:affiliationDepartment of Medicine, Division of Endocrinology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, A3060 Bethesda, MD 20814-4799, USA.lld:pubmed
pubmed-article:15149737pubmed:publicationTypeJournal Articlelld:pubmed