Modulation of ANF-R2/ANP-C receptors by angiotensin II in vascular smooth muscle cells.
In the present studies, we have investigated the modulation of atrial natriuretic factor (ANF) receptor of R2 subtype (ANF-R2) coupled to adenylyl cyclase/cAMP signal transduction system by angiotensin II (AII). C-ANF4-23 [C-ANF4-23, [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF4-23-NH2] and AII inhibited adenylyl cyclase activity in control vascular smooth muscle cells (VSMC A-10) by about 40% and 30% respectively. Pretreatment of the cells with AII resulted in the attenuation of both C-ANF4-23- and AII-mediated inhibition of adenylyl cyclase. Losartan treatment of the cells was able to partially block (approximately 50%) the AII- as well as C-ANF4-23-mediated inhibitions of adenylyl cyclase that are completely lost by AII pretreatment. The pretreatment of the cells with AII alone or with losartan did not affect the [125I]-ANF binding to ANF receptors. However, AII treatment resulted in the augmentation of the levels of Gi alpha 2 and Gi alpha 3. On the other hand, staurosporine (a protein kinase C [PKC] inhibitor) treatment of cells before AII treatment was able to prevent the attenuation of both C-ANF4-23 as well as AII-mediated inhibition of adenylyl cyclase elicited by AII. These results indicate that the AII modulation of ANF-R2 receptor-mediated inhibition of adenylyl cyclase is independent of ANF-R2 receptor density or the levels of Gi regulatory protein and may be due to the uncoupling of the ANF-R2 receptor from the Gi protein. This uncoupling may be associated with the phosphorylation of the Gi protein by PKC activated by AII.
Palaparti
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Department of Physiology, University of Montréal, Québec, Canada.
Anand-Srivastava
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MB
D000262:Adenylyl Cyclases / Q000032:analysis; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D006162:Guanylate Cyclase / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D019311:Staurosporine; D019808:Losartan