Sympathetic denervation impairs agonist-stimulated phosphatidylinositol metabolism in rat parotid glands.
Substance P, muscarinic and alpha-adrenoceptor agonists stimulated the incorporation of [3H]inositol into phosphatidylinositol in rat parotid gland slices. Surgical denervation of the sympathetic input to the rat parotid gland by superior cervical ganglionectomy produced marked reductions in these responses. The stimulated incorporation of radiolabelled precursors into phosphatidylinositol is a measure of its resynthesis after receptor-mediated breakdown of inositol phospholipids. We therefore examined the enzymic site of the lesion induced by sympathetic denervation using parotid gland slices labelled with either [3H]inositol or [32P]phosphate and stimulated with substance P. Receptor-activated phospholipase C attack upon [3H]inositol phospholipids was assayed by measuring the formation of [3H]inositol 1-phosphate in the presence of 10 mM-Li+ to inhibit further breakdown. It was not affected by denervation. Substance P elicited a rapid breakdown of phosphatidylinositol 4,5-bisphosphate and this response was reduced in the denervated gland. The second step in stimulated phosphatidylinositol turnover, phosphorylation of diacylglycerol to phosphatidate was not affected by denervation. Sympathetic denervation appears to induce a specific enzymic lesion in the parotid gland that impairs receptor-stimulated resynthesis of phosphatidylinositol from phosphatidate. This change in membrane lipid metabolism may be related to a number of the effects of sympathetic denervation, such as agonist supersensitivity, reduced gland cell proliferation and induction of new surface receptors.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology*; D013562:Sympathectomy
C011439:1,2-diacylglycerol; D004075:Diglycerides; D010710:Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D010656:Phenylephrine; D013373:Substance P; D007294:Inositol; D002217:Carbachol