Stimulation of phosphatidylinositol turnover in various tissues by cholinergic and adrenergic agonists, by histamine and by caerulein.

Abstract

Studies are reported of the biochemical and pharmacological characteristics of the stimulation of phosphatidylinositol metabolism that is produced in appropriate target tissues by stimulation of various receptors that use Ca(2+) as their second messenger. (1) Muscarinic cholinergic and alpha-adrenergic phosphatidylinositol responses were observed in rat lacrimal gland, and a response to caerulein was detected in the longitudinal smooth muscle of guinea-pig ileum. (2) The muscarinic cholinergic phosphatidylinositol response of rat lacrimal gland, like that of several other tissues, is not dependent on the availability of extracellular Ca(2+). (3) Three phosphatidylinositol responses, namely to histamine in guinea-pig ileum smooth muscle, to alpha-adrenergic stimulation in rat vas deferens and to muscarinic cholinergic stimulation in rat lacrimal gland, were all found to involve phosphatidylinositol breakdown. (4) The stereospecificity of the muscarinic receptor responsible for the phosphatidylinositol response of guinea-pig pancreas was tested by using the two stereoisomeric forms of acetyl-beta-methylcholine; the S-isomer was very much more active than the R-isomer in provoking both phosphatidylinositol breakdown and its labelling with (32)P, as it is in provoking other physiological responses such as contractility or secretion. (5) Pilocarpine, a muscarinic partial agonist, provoked a significantly smaller phosphatidylinositol breakdown in rat parotid fragments than did carbamoylcholine, a potent muscarinic agonist. (6) All of these results are consistent with, but do not prove, a previously offered hypothesis that suggests that phosphatidylinositol breakdown is a reaction essential to stimulus-response coupling at a variety of cell-surface receptors that mobilize Ca(2+) from and through the plasma membranes of target tissues.