Alpha 1-adrenergic receptor-mediated activation of phospholipase D in rat cerebral cortex.

摘要: We have investigated phospholipase D activity in rat brain cortical slices prelabeled with [32P]orthophosphoric acid. In the presence of ethanol (170 mM), norepinephrine stimulated, a dose-dependent manner (EC50 = 2.2 microM), accumulation [32P]phosphatidylethanol as result activity. Norepinephrine-stimulated was completely inhibited by prazosin, specific alpha 1-adrenergic antagonist (Ki 2.8 nM). However, no phosphatidylethanol observed muscarinic agonist carbachol. The Ca2+ ionophore ionomycin and protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also stimulated slices, dose- time-dependent manner, whereas inactive phorbol, 4 alpha-phorbol 12,13-didecanoate, did not stimulate Staurosporine 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two potent inhibitors C, PMA stimulation activity, but affect response to norepinephrine. Furthermore, effects were additive. Differences between found regard extracellular requirement time course accumulation. No from cerebellum, area low density receptors, while effect greater cerebellum than or hippocampal slices. These results strongly suggest that activation involve different mechanisms.