P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes.
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Abstract
Extracellular ATP modulates cardiac contraction through P2-purinoceptors on cardiac myocytes. To elucidate the molecular mechanism of this response, we examined the effects of P2-purinoceptor activation on phosphoinositide (PI) hydrolysis and the cAMP system in cultured ventricular myocytes of fetal mice. In a concentration-dependent manner, ATP stimulated accumulations of [3H]inositol monophosphate, bisphosphate, and trisphosphate with the half-maximum effective concentration of approximately 1 microM in the myocytes labeled with [3H]inositol. The order of efficacy of a series of adenyl compounds for stimulation of PI hydrolysis was adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ATP greater than ADP, 5'-adenylylimidodiphosphate (APPNP) greater than alpha,beta-methyleneadenosine 5'-triphosphate (APCPP) greater than beta,gamma-methyleneadenosine 5'-triphosphate, AMP greater than adenosine. On the other hand, 100 microM ATP gamma S inhibited isoproterenol-induced accumulation of cAMP by approximately 70% without decreasing the time to maximal cAMP levels, as measured by radioimmunoassay. This response was also concentration dependent, with a half-maximum inhibitory concentration (IC50) of approximately 1 microM. All of the tested ATP, ADP, and ATP analogues inhibited the cAMP system, and the responses to ATP gamma S, APPNP, and APCPP were insensitive to an A1-purinoceptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. Pertussis toxin attenuated the ATP-induced PI hydrolysis by no more than 25% at 100 ng/ml but completely suppressed the ATP gamma S-induced inhibition of the cAMP system.(ABSTRACT TRUNCATED AT 250 WORDS)
- Copyright © 1992 by American Heart Association
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- P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes.M Yamada, Y Hamamori, H Akita and M YokoyamaCirculation Research. 1992;70:477-485, originally published March 1, 1992https://doi.org/10.1161/01.RES.70.3.477
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