Alpha 1-adrenergic and muscarinic cholinergic stimulation of phosphoinositide hydrolysis in adult rat cardiomyocytes.

Abstract

Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores were labeled with [3H]inositol, and [3H]inositol phosphate formation was assessed after the addition of lithium chloride and norepinephrine. Norepinephrine increased the accumulation of [3H]inositol phosphate by approximately 5-fold, giving a maximal response at approximately 30 microM and a half-maximal response at approximately 1 microM. There was a significant increase in [3H]inositol phosphate formation in response to norepinephrine at 5 minutes, and the response was linear over 40 minutes. Norepinephrine-stimulated [3H]inositol phosphate formation was not blocked by propranolol (1 microM) or yohimbine (0.1 microM) but was completely antagonized by the alpha 1-selective antagonist prazosin (0.1 microM). Muscarinic cholinergic receptor activation by carbachol also stimulated [3H]inositol phosphate formation in rat ventricular myocytes. The maximal effect of carbachol (approximately 2-fold) was always less than that of norepinephrine. The combined effects of norepinephrine and carbachol were additive, suggesting that the two hormones do not share a common rate-limiting step. Removal of extracellular calcium and addition of ethylene glycol bis(beta-amino ether)-N,N'-tetraacetic acid, attenuated, but did not abolish, norepinephrine- or carbachol-stimulated [3H]inositol phosphate formation. Neither the calcium ionophore A23187 nor the calcium channel blockers verapamil and nifedipine had any effect on basal or hormone-stimulated [3H]inositol phosphate formation. We suggest that some of the physiological and metabolic effects of adrenergic and cholinergic stimulation on the rat myocardium are secondary to receptor-mediated hydrolysis of phosphoinositides.

Right atrial dilatation increases inositol‐(1,4,5)trisphosphate accumulation Implications for the control of atrial natriuretic peptide release

“…Stimulation was not secondary to release of neurotransmitters. Furthermore, Ptlns turnover in heart is not stimulated by increases in cytosolic calcium [2,5], making it unlikely that the response to dilatation is mediated by calcium. While mediation by some other change caused by dilatation cannot be ruled out, it remains possible that 'stretch receptors' can directly activate the Ptlns-(4,5)P2-specific phospholipase C.…”

“…The PtIns turnover pathway has been well studied in many tissues but relatively little detailed information is available for myocardial tissue. In isolated ventricular myocytes [2], ventricle strips [3], perfused ventricles [4] and intact perfused hearts [5], 2-4-fold stimulations by noradrenaline (c~t-receptors) and acetylcholine (muscarinic receptors) have been observed. In the present study isolated perfused rat hearts have been used to study the PtIns turnover response to right atrial distention, a stimulus known to cause release of atrial natriuretic peptide.…”

α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart

“…In the heart, the most extensively documented biochemical responses to ␣ 1 -adrenergic stimulation is G ␣q activation of phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate, which gives rise to 1,2-diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP 3 ), as well as to PKC activation by these second messengers (9,34).…”

Stimulation of phosphoinositide hydrolysis via class I antigen‐specific recognition in murine cardiac tissue

“…In addition to receptors that regulate cyclic AMP (cAMP) formation, there is another type of cell surface receptor which stimulates phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) [1]. Muscarinic cholinergic and al-adrenergic receptors of the heart are coupled to stimulated polyphosphoinositide turnover [2,3] and it has been suggested that some of the physiological and metabolic effects of adrenergic and cholinergic actions upon myocardium are secondary to receptorCorrespondence address: L. Sterin-Borda, Serrano 665, (1414) Buenos Aires, Argentina mediated hydrolysis of phosphoinositides [1,3]. Furthermore, it has been demonstrated that the products of phospholipase C hydrolysis, namely DG and PI3, may serve as intracellular second messengers.…”