期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 285, 期 1, 页码 H97-H103出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00956.2002
关键词
p38 mitogen-activated protein kinase; guanylyl cyclase; G(i) protein
资金
- NHLBI NIH HHS [HL-48839] Funding Source: Medline
Adenosine A(1) receptor activation causes protein phosphatase 2a (PP2a) activation in ventricular myocytes. This attenuates beta-adrenergic functional effects in the heart (Liu Q and Hofmann PA. Am J Physiol Heart Circ Physiol 283: H1314-H1321, 2002). The purpose of the present study was to identify the signaling pathway involved in the translocation/activation of PP2a by adenosine A(1) receptors in ventricular myocytes. We found that N-6-cyclopentyladenosine (CPA; an adenosine A(1) receptor agonist)-induced PP2a translocation was blocked by p38 MAPK inhibition but not by JNK inhibition. CPA increased phosphorylation of p38 MAPK, and this effect was abolished by pertussis toxin and inhibitors of the cGMP pathway. Moreover, CPA-induced PP2a translocation was blocked by inhibition of the cGMP pathway. Guanylyl cyclase activation mimicked the effects of CPA and caused p38 MAPK phosphorylation and PP2a translocation. Finally, CPA-induced dephosphorylations of troponin I and phospholamban were blocked by pertussis toxin and attenuated by p38 MAPK inhibition. These results suggest that adenosine A(1) receptor-mediated PP2a activation uses a pertussis toxin-sensitive G(i) protein-guanylyl cyclase-p38 MAPK pathway. This proposed, novel pathway may play a role in acute modulation of cardiac function.
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