Angiotensin II modulates ANP-R2/ANP-C receptor-mediated inhibition of adenylyl cyclase in vascular smooth muscle cells: role of protein kinase C. 1998

A Palaparti, and M B Anand-Srivastava
Groupe de recherche sur le système nerveux autonome, and Department of Physiology, University of Montreal, Montreal, Quebec, H3C 3J7, Canada.

In the present studies, we have investigated the modulation of atrial natriuretic peptide (ANP) receptor of R2 subtype (ANP-R2/ANP-C) coupled to adenylyl cyclase/cAMP signal transduction system by angiotensin II (angII). C-ANF4-23 [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF4-23-NH2] and AngII inhibited adenylyl cyclase activity in a concentration-dependent manner in vascular smooth muscle cells (VSmc A-10). The maximal inhibitions observed were about 40 and 30%, respectively, with an apparent Ki of about 1 and 10 nm. Pretreatment of the cells with AngII resulted in the attenuation of both C-ANF4-23 and AngII-mediated inhibitions of adenylyl cyclase, without altering [125I]-ANF binding. The levels of Gialpha-2 and Gialpha-3 proteins as determined by immunoblotting were also augmented by AngII treatment. In addition, AngII treatment stimulated the phosphorylation of Gialpha2 but not of Gialpha3 or ANP-C receptor, as revealed by immunoprecipitation of the proteins using specific antibodies after prelabelling the cells with [32P]orthophosphate. Staurosporine and chelerythrine, protein kinase C (PKC) inhibitors at 1 and 100 nm, respectively, prevented the AngII-mediated desensitization of C-ANF 4-23-sensitive adenylyl cyclase. In addition, the AngII-mediated phosphorylation of Gialpha2 protein was also inhibited partially by about 35% by staurosporine treatment. These results suggest that the attenuation of C-ANF4-23-mediated inhibition of adenylyl cyclase activity by AngII may not be attributed to the downregulation of receptors or to the decreased levels of G-proteins, and may involve PKC-dependent mechanisms.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010617 Phenanthridines
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006162 Guanylate Cyclase An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate
D000067956 Adenylyl Cyclase Inhibitors Compounds that bind to and inhibit the action of ADENYLYL CYCLASES. Adenylate Cyclase Inhibitors,Cyclase Inhibitors, Adenylate,Cyclase Inhibitors, Adenylyl,Inhibitors, Adenylate Cyclase,Inhibitors, Adenylyl Cyclase
D000470 Alkaloids Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed) Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine

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