Activation of phosphatidylcholine-selective phospholipase C by I1-imidazoline receptors in PC12 cells and rostral ventrolateral medulla.
The I1-imidazoline receptor is expressed in the rostral ventrolateral medulla (RVLM) where it mediates vasodepression, and in PC12 pheochromocytoma cells where it elicits generation of diacylglycerol independent of phosphatidylinositol turnover or activation of phospholipase D. We hypothesized that the I1-imidazoline receptor couples to a phosphatidylcholine-selective phospholipase C (PC-PLC). The I1-agonist moxonidine elicited diacyglyceride accumulation and release of [3H]phosphocholine from PC12 cells prelabeled with [3H]choline. The PC-PLC inhibitor D609 abolished both responses. Microinjection of D609 into the RVLM of hypertensive rats blocked the vasodepressor response to intravenous moxonidine. These data implicate PC-PLC in cellular and organismic responses to I1-receptor stimulation.
Separovic
D
D
Department of Medicine, Case Western Reserve School of Medicine, Cleveland, OH 44106-4982, USA.
Kester
M
M
Haxhiu
M A
MA
Ernsberger
P
P
D000310:Adrenal Gland Neoplasms; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008526:Medulla Oblongata / Q000201:enzymology / Q000502:physiology*; D008845:Microinjections; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology; D009636:Norbornanes; D016716:PC12 Cells; D010673:Pheochromocytoma; D051381:Rats; D011918:Rats, Inbred SHR; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D013859:Thiocarbamates; D013871:Thiones / Q000008:administration & dosage / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000959:Antihypertensive Agents; D001952:Bridged-Ring Compounds; D004075:Diglycerides; D007093:Imidazoles; D054755:Imidazoline Receptors; D009414:Nerve Growth Factors; D009636:Norbornanes; D011955:Receptors, Drug; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; C043482:moxonidine; D010738:Type C Phospholipases