Dohi T, Itadani K, Yamaki H, Akagawa Y, Morita K, Kitayama S
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
J Dent Res. 1997 Jan;76(1):568-74. doi: 10.1177/00220345970760010701.
Platelet-activating factor (PAF), a phospholipid mediator exhibiting potent biological activities, has been shown to stimulate amylase release from the pancreas and salivary glands. The capacity of salivary glands for PAF biosynthesis in response to stimulation has also been demonstrated. To elucidate the role of PAF in salivary glands, we studied the regulation of platelet-activating factor synthesis by the autonomic nervous system in canine salivary glands. Acetylcholine and ionomycin stimulated PAF production in dispersed cells from parotid, submandibular, and sublingual glands of dogs. Norepinephrine and phenylephrine, but not isoproterenol, also stimulated PAF production in submandibular gland cells. Norepinephrine-induced PAF production was blocked by phentolamine but not by propranolol. Acetylcholine and norepinephrine increased both the PAF production and liberation of [14C]arachidonic acid from cells pre-labeled with [14C]arachidonic acid in the presence of Ca2+ in the medium. These stimulants increased [14C]arachidonic acid liberation without the accompanying production of PAF in Ca(2+)-deprived medium. No activators or inhibitors of protein kinase C produced or affected acetylcholine-induced PAF production. Lyso-PAF:acetyl-CoA acetyltransferase was activated in the cells treated with acetylcholine, norepinephrine, isoproterenol, and 8Br-cyclic AMP. Deprivation of Ca2+ in the medium markedly reduced acetylcholine-induced activation of the transferase, but little affected norepinephrine-, isoproterenol-, and 8Br-cyclic AMP-induced activation. Dithiothreitol-insensitive cholinephosphotransferase activity was also increased by acetylcholine, norepinephrine, isoproterenol, and 8Br-cyclic AMP, and the deprivation of Ca2+ in the medium further increased the activation of the enzyme activity by these agents. These results suggest that PAF synthesis in canine salivary glands is under the control of muscarinic cholinergic and alpha-adrenergic systems via Ca(2+)-dependent remodeling pathways, and that the independent activation of either phospholipase A2 or acetyltransferase is insufficient for PAF production in submandibular gland cells, i.e., the concurrent activation of these enzymes is required.
血小板活化因子（PAF）是一种具有强大生物活性的磷脂介质，已被证明能刺激胰腺和唾液腺释放淀粉酶。唾液腺在受到刺激时生物合成PAF的能力也已得到证实。为了阐明PAF在唾液腺中的作用，我们研究了自主神经系统对犬唾液腺中血小板活化因子合成的调节。乙酰胆碱和离子霉素刺激了犬腮腺、颌下腺和舌下腺分散细胞中PAF的产生。去甲肾上腺素和苯肾上腺素，而非异丙肾上腺素，也刺激了颌下腺细胞中PAF的产生。酚妥拉明可阻断去甲肾上腺素诱导的PAF产生，但普萘洛尔不能。在培养基中存在Ca2+的情况下，乙酰胆碱和去甲肾上腺素增加了预先用[14C]花生四烯酸标记的细胞中PAF的产生以及[14C]花生四烯酸的释放。在无Ca2+的培养基中，这些刺激物增加了[14C]花生四烯酸的释放，但未伴随PAF的产生。蛋白激酶C的激活剂或抑制剂均未产生或影响乙酰胆碱诱导的PAF产生。溶血PAF：乙酰辅酶A乙酰转移酶在用乙酰胆碱、去甲肾上腺素、异丙肾上腺素和8-溴环磷酸腺苷处理的细胞中被激活。培养基中Ca2+的缺失显著降低了乙酰胆碱诱导的转移酶激活，但对去甲肾上腺素、异丙肾上腺素和8-溴环磷酸腺苷诱导的激活影响较小。二硫苏糖醇不敏感的胆碱磷酸转移酶活性也被乙酰胆碱、去甲肾上腺素、异丙肾上腺素和8-溴环磷酸腺苷增加，培养基中Ca2+的缺失进一步增强了这些试剂对该酶活性的激活。这些结果表明，犬唾液腺中PAF的合成受毒蕈碱胆碱能和α-肾上腺素能系统通过Ca2+依赖性重塑途径的控制，并且在颌下腺细胞中，单独激活磷脂酶A2或乙酰转移酶不足以产生PAF，即这些酶需要同时激活。
