Histamine increases phospholipid methylation and H2-receptor-adenylate cyclase coupling in rat brain.
Histamine stimulated the enzymatic synthesis of phosphatidylcholine from phosphatidylethanolamine in crude synaptic membranes of rat brain containing the methyl donor S-adenosyl-L-methionine (SAM). In the presence of, but not in the absence of SAM, histamine increased cyclic AMP accumulation at the concentrations that stimulate phospholipid methylation. S-Adenosyl-L-homocysteine, an inhibitor of phospholipid methyltransferases, inhibited histamine-stimulated phospholipid methylation and histamine-induced cyclic AMP accumulation in the presence of SAM in a concentration-dependent manner. Histamine-induced [3H]methyl incorporation into phospholipids exhibited a marked regional heterogeneity in rat brain in the order of cortex greater than medulla oblongata greater than hippocampus greater than striatum greater than midbrain greater than hypothalamus. The regional distribution of histamine-induced cyclic AMP accumulation exactly paralleled histamine-stimulated [3H]methyl incorporation in rat brain. Histamine-induced cyclic AMP accumulation was inhibited by the addition of cimetidine or famotidine, but not by mepyramine or diphenhydramine. The accumulation of cyclic AMP in the presence of SAM was observed by the addition of impromidine or dimaprit, but not by 2-pyridylethylamine. These results indicate that phospholipid methylation is induced by histamine and may participate in H2-receptor-mediated stimulation of adenylate cyclase in rat brain.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism; D014018:Tissue Distribution
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011970:Receptors, Histamine H2; D012436:S-Adenosylmethionine; D006632:Histamine; D012435:S-Adenosylhomocysteine; D000242:Cyclic AMP; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D000262:Adenylyl Cyclases