Aging of rat heart myocytes disrupts muscarinic receptor coupling that leads to inhibition of cAMP accumulation and alters the pathway of muscarinic-stimulated phosphoinositide hydrolysis.

Biochemistry
E Moscona-AmirM Sokolovsky

Abstract

The biochemical responses to muscarinic stimulation (inhibition of isoproterenol-stimulated cAMP accumulation and stimulation of phosphoinositide turnover) were investigated in intact myocyte cultures prepared from the hearts of newborn rats. The studies employed young (5 days after plating) and aged (14 days old) myocyte cultures. Aging of the myocyte cultures was accompanied by marked alterations in both the inhibition of cAMP accumulation and the stimulation of the phosphoinositide metabolism via the muscarinic receptors. However, the effects on the two muscarinic responses were different. The first response was disrupted at the level of the coupling of the muscarinic receptors with adenylate cyclase through Gi. On the other hand, muscarinic stimulation of phosphoinositide hydrolysis still occurred in the aged myocyte cultures; however, the inositol trisphosphate generated was not converted to inositol 1-phosphate as in young cultures or as in aged cultures stimulated by norepinephrine. This raises the possibility that muscarinic activation of aged myocyte cultures shifts the metabolic state of the cells and alters the pathway of phosphoinositide hydrolysis. Treatment of aging cultures with phosphatidylcholine liposomes unde...Continue Reading

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Citations

Apr 30, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Jaromir MyslivecekJan Ricny
Jan 23, 1990·European Journal of Pharmacology·R GalronM Sokolovsky
Jan 11, 1994·Biochimica Et Biophysica Acta·J Bothmer, J Jolles
Apr 21, 1998·Molecular and Cellular Endocrinology·M M FacchinettiA R de Boland
Sep 28, 1990·Biochemical and Biophysical Research Communications·R GalronM Sokolovsky
Sep 15, 1989·Biochemical and Biophysical Research Communications·R GalronM Sokolovsky
Jul 22, 2016·British Journal of Pharmacology·Louise E See HoeJason N Peart
Dec 1, 1992·Journal of Neurochemistry·R Pinkas-KramarskiM Sokolovsky

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