STIMULATION OF PLATELET-ACTIVATING-FACTOR SYNTHESIS BY NEUROTRANSMITTERS IN SALIVARY-GLANDS

Platelet-activating factor (PAF), a phospholipid mediator exhibiting p otent biological activities, has been shown to stimulate amylase relea se from the pancreas and salivary glands. The capacity of salivary gla nds for PAF biosynthesis in response to stimulation has also been demo nstrated. To elucidate the role of PAF in salivary glands, we studied the regulation of platelet-activating factor synthesis by the autonomi c nervous system in canine salivary glands. Acetylcholine and ionomyci n stimulated PAF production in dispersed cells from parotid, submandib ular, and sublingual glands of dogs. Norepinephrine and phenylephrine, but not isoproterenol, also stimulated PAF production in submandibula r gland cells. Norepinephrine-induced PAF production was blocked by ph entolamine but not by propranolol. Acetylcholine and norepinephrine in creased both the PAF production and liberation of [C-14]arachidonic ac id from cells pre-labeled with [C-14]arachidonic acid in the presence of Ca2+ in the medium. These stimulants increased [C-14]arachidonic ac id liberation without the accompanying production of PAF in Ca2+-depri ved medium. No activators or inhibitors of protein kinase C produced o r affected acetylcholine-induced PAF production. Lyso-PAF:acetyl-CoA a cetyltransferase was activated in the cells treated with acetylcholine , norepinephrine, isoproterenol, and 8Br-cyclic AMP. Deprivation of Ca 2+ in the medium markedly reduced acetylcholine-induced activation of the transferase, but little affected norepinephrine-, isoproterenol-, and 8Br-cyclic AMP-induced activation. Dithiothreitol-insensitive chol inephosphotransferase activity was also increased by acetylcholine, no repinephrine, isoproterenol, and 8Br-cyclic AMP, and the deprivation o f Ca2+ in the medium further increased the activation of the enzyme ac tivity by these agents. These results suggest that PAF synthesis in ca nine salivary glands is under the control of muscarinic cholinergic an d alpha-adrenergic systems via Ca2+-dependent remodeling pathways, and that the independent activation of either phospholipase A(2) or acety ltransferase is insufficient for PAF production in submandibular gland cells, i.e., the concurrent activation of these enzymes is required.