Stimulated phosphatidylinositol breakdown, followed by compensatory resynthesis, is a response of a wide variety of cells to many hormones and neurotransmitters. Until recently, most work on this response employed secretory tissues, nervous tissues or smooth muscles, and the most intensively studied stimuli were muscarinic, cholinergic and a-adrenergic. As a tentative synthesis of all of these past studies, we have developed the view that there is a family of cell-surface receptors that all act upon their target cells to cause a rise in the cytosolic Ca2+ concentration. We suggested that phosphatidylinositol breakdown might be a reaction intrinsic to some unitary mechanism whereby these receptors bring about Ca2+ mobilization (Michell, 1975, 1979a, b, c; Michell et al., 1977; Jones et a [., 1979).

In its most general interpretation, this hypothesis predicts that stimulation of phosphatidylinositol breakdown (and, secondarily, its resynthesis) should always accompany hormone-stimulated Ca2+ mobilization. Since the majority of studies of stimulated phosphatidylinositol metabolism have previously used tissue fragments, it seemed appropriate to test this prediction in isolated hepatocytes, a dispersed cell system that is amenable to many types of biochemical investigation. We have therefore demonstrated stimulation of phosphatidylinositol metabolism in isolated rat hepatocytes exposed to three glycogenolytic hormones whose actions appear to be mediated by Ca2+ ions, namely vasopressin, angiotensin and adrenaline acting through a-receptors (Kirk et al., 1977, 1978, 1979; Billah & Michell, 1978, 1979): the possibility that there might be such an a-adrenergic response was previously suggested by De Torrentegui & Berthet (1966). Studies with an a-adrenergic antagonist and an angiotensin antagonist have established that the three hormones act at three different receptors (Kirk et al., 1977; Billah & Michell, 1978, 1979). Glucagon, another hormone that is glycogenolytic but whose actions are mediated through cyclic AMP, had no effect on phosphatidylinositol metabolism in either liver slices or hepatocytes (De Torrentegui & Berthet, 1966; Kirk et af., 1977).