Study of receptor-stimulated phosphatidylinositol hydrolysis in intact, perfused rat hearts

1. Phosphatidylinositol turnover has been measured in intact, perfused rat hearts by measuring generation of inositol phosphates following [3H]-inositol labelling. Stimulation of accumulations of inositol monophosphate, inositol bisphosphate and inositol trisphosphate were observed during perfusion with either noradrenaline (3 X 10(-5) mol/l) or carbachol (10(-3) mol/l). 2. Stimulation by noradrenaline was antagonized by prazosin (10(-7) mol/l) but not by propranolol (10(-7) mol/l), indicating mediation via alpha 1-adrenoceptors. Stimulation by carbachol was antagonized by atropine (10(-7) mol/l). 3. Transmural electrical stimulation of the hearts failed to increase inositol phosphate accumulation through alpha 1-adrenoceptors. A small stimulation mediated by muscarinic receptors was observed. Therefore alpha 1-adrenoceptors which stimulate phosphatidylinositol turnover probably do not have a synaptic localization in heart. 4. The development of methods for the study of phosphatidylinositol turnover in intact hearts will facilitate an investigation of relationships between this signal transduction pathway and cardiac function.