Phosphatidylcholine breakdown in rat liver plasma membranes. Roles of guanine nucleotides and P2-purinergic agonists.
Release of P-choline and choline from purified rat plasma membrane preparations was increased by GTP and its less hydrolyzable analogues, whereas other nucleotide triphosphates had little or no effect. Stimulation by guanosine 5'-(3-O-thiol)triphosphate (GTP gamma S) was dependent upon magnesium, inhibited by guanosine 5'-(2-O-thiol)diphosphate, and independent of calcium. ATP and ADP (1-100 microM) markedly enhanced the GTP gamma S stimulation of P-choline plus choline release but had no effect alone. ADP was as effective as ATP and nonhydrolyzable ATP analogues produced a similar or greater stimulation, whereas AMP and adenosine were much less effective. Vasopressin (0.1 microM) also produced a small stimulation. Under conditions in which protein kinase C was activated, PMA also stimulated the response to GTP gamma S but was ineffective in its absence. P-choline was the initial product which was hydrolyzed to choline. Guanine nucleotide and purinergic effects were also apparent on phosphatidylcholine degradation. EGTA, at 0.5 mM, completely removed purinergic stimulation but did not affect P-choline plus choline released in response to GTP gamma S alone. Prior treatment of plasma membranes with cholera toxin or prior injection of animals with islet-activating protein did not affect the stimulation of P-choline plus choline release either by GTP gamma S alone or by GTP gamma S plus ATP. These results indicate that a phosphatidylcholine phospholipase C is coupled to purinergic receptors in rat liver plasma membranes by a GTP-binding protein. Hydrolysis of phosphatidylcholine could contribute to hepatic diacylglycerol levels and thus influence protein kinase C activity.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D014316:Tritium
D000227:Adenine Nucleotides; D004983:Ethanolamines; D006150:Guanine Nucleotides; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D014316:Tritium; D019856:Ethanolamine; D002794:Choline