This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Orlov, S. N. Articles by Hamet, P. Search for Related Content PubMed PubMed Citation Articles by Orlov, S. N. Articles by Hamet, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

(Hypertension. 1996;27:774-780.)
© 1996 American Heart Association, Inc.

Articles

cAMP Signaling Inhibits Dihydropyridine-Sensitive Ca²⁺ Influx in Vascular Smooth Muscle Cells

Sergei N. Orlov; Johanne Tremblay; Pavel Hamet

From the Centre de Recherche Hôtel-Dieu de Montréal, Université de Montréal (Québec), Canada.

Correspondence to Pavel Hamet, MD, PhD, Laboratory of Molecular Pathophysiology, Centre de Recherche Hôtel-Dieu de Montréal, 3850 St. Urbain St, Montréal, Québec H2W 1T8, Canada.

Abstract This study examines the role of the cAMP signaling pathway in the regulation of ⁴⁵Ca influx in cultured vascular smooth muscle cells from the rat aorta. K⁺_o-induced depolarization of smooth muscle cells increased the rate of ⁴⁵Ca uptake by twofold to threefold. This effect was completely abolished by the dihydropyridine derivatives nifedipine and nicardipine, with a K_i of 3 and 10 nmol/L, respectively. Activators of cAMP signaling (isoproterenol, forskolin, cholera toxin) increased cAMP content by 50- to 100-fold and decreased voltage-dependent ⁴⁵Ca uptake by 50% to 70%. Neither the dihydropyridines nor the cAMP activators affected basal ⁴⁵Ca influx. Direct addition of the protein kinase inhibitor H-89 to the incubation medium in the 1- to 10-µmol/L range did not alter basal ⁴⁵Ca uptake but completely abolished voltage-dependent Ca²⁺ transport. Preincubation of cells for 1 hour with 10 µmol/L H-89 did not modify basal and depolarization-induced ⁴⁵Ca uptake in H-89–free medium but prevented forskolin-induced inhibition of voltage-dependent Ca²⁺ influx. The addition of cytoskeleton-active compounds reduced voltage-dependent Ca²⁺ transport and completely abolished its regulation by cAMP. Activation of cAMP signaling decreased the volume of smooth muscle cells by 12% to 15%. The same cell volume diminution in hyperosmotic medium did not alter voltage-dependent ⁴⁵Ca uptake. Thus, data obtained in this study show that in contrast to cardiac and skeletal myocytes, in vascular smooth muscle cells, ⁴⁵Ca influx, putatively due to L-type channels, is inhibited by cAMP. This regulatory pathway appears to be mediated via protein kinase A activation and cytoskeleton reorganization.

Key Words: muscle, smooth, vascular • calcium channels • cyclic AMP • cytoskeleton

This article has been cited by other articles:

				M Hennenberg, J Trebicka, T Sauerbruch, and J Heller Mechanisms of extrahepatic vasodilation in portal hypertension Gut, September 1, 2008; 57(9): 1300 - 1314. [Abstract] [Full Text] [PDF]

				H.-Y. Zhang, Y. Shirasawa, X. Chen, H. Yu, and J. N. Benoit Impaired agonist-dependent myosin phosphorylation and decreased RhoA in rat portal hypertensive mesenteric vasculature Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G603 - G608. [Abstract] [Full Text] [PDF]

				A. R. Gosmanov, Z. Fan, X. Mi, E. G. Schneider, and D. B. Thomason ATP-sensitive potassium channels mediate hyperosmotic stimulation of NKCC in slow-twitch muscle Am J Physiol Cell Physiol, March 1, 2004; 286(3): C586 - C595. [Abstract] [Full Text]

				S. Taurin, N. O Dulin, D. Pchejetski, R. Grygorczyk, J. Tremblay, P. Hamet, and S. N Orlov c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium-mediated, calcium-independent mechanism J. Physiol., September 15, 2002; 543(3): 835 - 847. [Abstract] [Full Text] [PDF]

				K. E. PURDY and W. J. ARENDSHORST Iloprost Inhibits Inositol-1,4,5-Trisphosphate-Mediated Calcium Mobilization Stimulated by Angiotensin II in Cultured Preglomerular Vascular Smooth Muscle Cells J. Am. Soc. Nephrol., January 1, 2001; 12(1): 19 - 28. [Abstract] [Full Text]

				K. L. Dodge, D. W. Carr, and B. M. Sanborn Protein Kinase A Anchoring to the Myometrial Plasma Membrane Is Required for Cyclic Adenosine 3',5'-Monophosphate Regulation of Phosphatidylinositide Turnover Endocrinology, November 1, 1999; 140(11): 5165 - 5170. [Abstract] [Full Text]

				M. S. Taylor and J. N. Benoit Effect of milrinone on small mesenteric artery vasoconstriction: role of K+ channels Am J Physiol Gastrointest Liver Physiol, July 1, 1999; 277(1): G69 - G78. [Abstract] [Full Text] [PDF]

				J. D. STOCKAND and S. C. SANSOM Glomerular Mesangial Cells: Electrophysiology and Regulation of Contraction Physiol Rev, July 1, 1998; 78(3): 723 - 744. [Abstract] [Full Text] [PDF]

				S. Uhlig, R. L. Featherstone, H.-D. Held, R. Nüsing, C. Schudt, and A. Wendel Attenuation by Phosphodiesterase Inhibitors of Lipopolysaccharide-Induced Thromboxane Release and Bronchoconstriction in Rat Lungs J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1453 - 1459. [Abstract] [Full Text]

				N. O. Dulin, J. Niu, D. D. Browning, R. D. Ye, and T. Voyno-Yasenetskaya Cyclic AMP-independent Activation of Protein Kinase A by Vasoactive Peptides J. Biol. Chem., June 8, 2001; 276(24): 20827 - 20830. [Abstract] [Full Text] [PDF]