α1-adrenoceptor-mediated formation of glycerophosphoinositol 4-phosphate in rat heart:: Possible role in the positive inotropic response

In the present study, we investigated whether phospholipase A(2) (PLA(2))/lysophospholipase activity producing glycerophosphoinositols from phosphoinositides was operating in rat heart and could be stimulated by alpha(1)-adrenergic agonists. PLA,/lysophospholipase activity was found in homogenates from rat right ventricles. The stimulation of PLA,/lysophospholipase activity by noradrenaline (NA) was prevented either by the a,alpha(1)-adrenergic antagonist prazosin or arachidonyl trifluoromethyl ketone, a selective inhibitor of the 85-110 kDa, sn-2-arachidonyl-specific cytosolic PLA(2). The selective alpha(1)-adrenergic agonist phenylephrine induced a concentration- and time-dependent increase in glycerophosphoinositol (GroPIns) and glycerophosphoinositol 4-phosphate (GroPIns4P) in rat right ventricle slices prelabelled with D-myo-[H-3]inositol. In electrically driven strips of rat right ventricles, prelabelled with D-myo-[3H]inositol, the positive inotropic effect induced by 20 mu M NA in the presence of propranolol was accompanied by the formation of GroPIns and GroPIns4P. The concentration of the formed GroPIns4P (1.33 -/+ 0.12 mu M, N = 6) was Similar to that previously reported to inhibit the Na+/Ca2+ exchanger in cardiac sarcolemmal vesicles (Luciani S, Antolini M, Bova S, Cargnelli G, Cusinato F, Debetto P, Trevisi L and Varotto R, Biochem Biophys Res Commun 206: 674-680, 1995). These findings show that the stimulation of cr, adrenoceptors in rat heart is followed by an increase in the formation of GroPIns4P, which may contribute to the positive inotropic effect of alpha(1)-adrenergic agonists by inhibition of the Na+/Ca2+ exchanger. (C) 1999 Elsevier Science Inc.