Norepinephrine-induced phosphatidylcholine hydrolysis by phospholipases D and C in rat tail artery.
Rat tail arterial segments were incubated with [3H]choline to selectively label endogenous phosphatidylcholine. Norepinephrine (NE; 10(-5) M) addition for periods of 10 s to 30 min significantly increased the concentration of extracellular phosphatidylcholine metabolites, [3H]choline, and [3H]phosphocholine. The release of [3H]choline and [3H]phosphocholine from the segments was NE dose dependent (10(-6)-10(-3) M). NE also increased the formation of [3H]phosphatidylethanol in [3H]myristate-labeled tail artery in the presence of ethanol, characteristic of phospholipase D activity. NE-induced phosphatidylcholine hydrolysis was blocked by pretreatment with prazosin (10(-5) M) and was unchanged by pretreatment with propranolol (10(-5) M). 4 beta-phorbol 12,13-dibutyrate (PDBu, 10(-6) M) stimulated the release of [3H]choline, which was inhibited by pretreatment with staurosporine (10(-5) M). The stimulatory effect of NE on phosphatidylcholine metabolism was not altered by either pretreatment with staurosporine (10(-5) M) or calcium-free buffer. In summary, we have demonstrated NE-stimulated phosphatidylcholine hydrolysis by phospholipase D and C in intact vascular smooth muscle. This effect of NE was dose dependent and was mediated through the alpha 1-adrenergic receptor. Norepinephrine and PDBu stimulated phosphatidylcholine hydrolysis through different mechanism(s), and the stimulatory effect of NE did not seem to require protein kinase C and calcium influx.
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Bockus Research Institute, Graduate Hospital, Philadelphia, Pennsylvania 19146.
Trajkovic
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LaBelle
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D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000201:enzymology*; D002462:Cell Membrane / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail; D010738:Type C Phospholipases / Q000378:metabolism*
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010767:Phosphorylcholine; D000431:Ethanol; D011433:Propranolol; D010738:Type C Phospholipases; D010739:Phospholipase D; D002794:Choline; D009638:Norepinephrine