Specific activation of adenylyl cyclase V by a purinergic agonist

FEBS Letters

Jaconi, Marisa¹  Pucéat, Michel¹  Vassort, Guy¹  Bony, Claire¹ 

[1] INSERM U-390, Laboratoire de Physiopathologie Cardiovasculaire, C.H.U. Arnaud de Villeneuve, 34295 Montpellier Cedex, France

关键词: ATP;    Adenylyl cyclase;    Cardiomyocyte;    Heart failure;   

DOI  :  10.1016/S0014-5793(98)00747-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The present study was designed to investigate whether and how the purinergic stimulation of rat ventricular myocytes modulates the cAMP-dependent pathway. Stimulation of cardiomyocytes with ATPγS in the presence of the phosphodiesterase inhibitor IBMX increases by 3-fold intracellular cAMP content. In contrast to β-adrenergic stimulation, the purinergic stimulation of adenylyl cyclase was not inhibited by activation or enhanced by inhibition of a G_i protein. Forskolin did not potentiate the effect of extracellular ATPγS on intracellular cAMP content but the effect of isoproterenol did. Like isoproterenol, the purinergic agonist decreased subsequent ADP-ribosylation of a 45 kDa G_αs by cholera toxin. ATPγS also increased cAMP content in neonatal rat cardiomyocytes, a cell type that expresses a long form of G_s protein (α_s, 52 kDa) in contrast to adult rat cardiomyocytes that express mostly a short form of G_s protein (α_s, 45 kDa). Both purinergic and β-adrenergic agonists increased cAMP in HEK 293 cells expressing type V adenylyl cyclase while cAMP was only increased by β-adrenergic stimulation of HEK expressing type IV or VI adenylyl cyclases. Thus, we propose that the purinergic and β-adrenergic stimulations differentially activate adenylyl cyclase isoforms in rat cardiomyocytes and that adenylyl cyclase V is the specific target of the purinergic stimulation.

【 授权许可】

Unknown