Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells
| Autor: | J. Zhang, Steven W. Kubalak, Stephen M. Lanier, M. Sato, Jerry G. Webb, E. Duzic |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Vasopressin medicine.medical_specialty Vascular smooth muscle Calmodulin Physiology Stimulation Biology In Vitro Techniques ADCY10 Muscle Smooth Vascular Adenylyl cyclase Rats Sprague-Dawley chemistry.chemical_compound Physiology (medical) Internal medicine medicine Cyclic AMP Animals Aorta Cells Cultured Protein Kinase C Vasopressin receptor Arginine vasopressin receptor 1A Angiotensin II Isoproterenol Rats Arginine Vasopressin Isoenzymes Endocrinology chemistry cardiovascular system biology.protein Calcium Cardiology and Cardiovascular Medicine hormones hormone substitutes and hormone antagonists Antidiuretic Hormone Receptor Antagonists Adenylyl Cyclases |
| Zdroj: | The American journal of physiology. 273(2 Pt 2) |
| ISSN: | 0002-9513 |
| Popis: | The influence of arginine vasopressin (AVP) on agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in vascular smooth muscle cells (VSMC) cultured from rat thoracic aorta. Incubation of VSMC with AVP for 60 s produced a 2- to 2.5-fold enhancement of isoproterenol-induced cAMP formation. AVP also increased cAMP stimulation by the prostaglandin I2 analogue iloprost. The effect of AVP to enhance agonist-stimulated cAMP formation was completely inhibited in cells pretreated with a selective antagonist of V1 vasopressin receptors but was not affected by blockade of V2 receptors. Inhibition of protein kinase C activation failed to alter the action of AVP to potentiate cAMP stimulation, but treatment of cells with calmodulin antagonists significantly attenuated this effect of the peptide. Moreover, depletion of Ca2+ stores with thapsigargin decreased AVP enhancement of isoproterenol-stimulated cAMP by > 70%. The action of AVP to increase cAMP stimulation was also demonstrated in freshly isolated strips of rat aorta where treatment with peptide produced a twofold increase in isoproterenol-stimulated cAMP formation. RNA blot analysis indicated expression in VSMC of mRNA encoding type III adenylyl cyclase, a Ca(2+)-calmodulin-sensitive isoform of the effector. Furthermore, when detergent-solubilized membrane extract was subjected to calmodulin affinity chromatography, a peak of adenylyl cyclase activity was identified which had affinity for calmodulin matrix in the presence of Ca2+. The results indicate that AVP activates V1 receptors in VSMC to enhance agonist-stimulated cAMP formation by a Ca(2+)-calmodulin-dependent mechanism and suggest that type III adenylyl cyclase may provide a focal point in the VSMC for cross talk between constrictor and dilator pathways. |
| Databáze: | OpenAIRE |
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