Histamine-induced release of arachidonic acid and of prostaglandins in the peripheral vascular bed: mode of action.
1. Injection or infusion of histamine intraarterially into the isolated perfused rabbit ear dose-dependently stimulated the release of prostaglandins (PGs) as measured by radioimmunoassay (PGE), bovine coronary artery strips (PGI2) and by the prelabeling technic with [1-14C]-arachidonic acid (PGI2, PGE2, PGF2 alpha, PGD2). 2. PG release was abolished by indometacin (1-3 microgram/ml) and reduced by the phospholipase A2 inhibitor quinacrine (10 microgram/ml) as well as by perfusing with calcium-free, 1 mM EGTA containing solution. 3. The histamine H2-receptor antagonists burimamide (5 microgram/ml) and cimetidine (2 microgram/ml) did not influence histamine-induced PG release. The H1-receptor antagonist mepyramine (0.1-1 microgram/ml) abolished histamine-induced mepyramine (0.1-1 microgram/ml) abolished histamine-induced PG release. 4. In the presence, but not in the absence, of bovine serum albumin there was a basal release of high amounts of arachidonic acid. Histamine tended to increase the released amount of radioactive arachidonic acid. In contrast to indometacin which only blocked PG release, mepyramine significantly reduced the histamine-stimulated release of arachidonic acid, too. 5. The results show that in the peripheral vascular bed, histamine, via H1-receptors, activates a phospholipase A2 mainly by increasing a transfer of extracellular calcium into the cell. Activation of a phospholipase A2 results in the release of arachidonic acid possibly from a rather small endogenous pool which specifically provides substrate for the PG synthetase system.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D004423:Ear / Q000098:blood supply; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D011969:Receptors, Histamine H1 / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism
D001095:Arachidonic Acids; D006634:Histamine H1 Antagonists; D011453:Prostaglandins; D011969:Receptors, Histamine H1; D013928:Thromboxane A2; D006632:Histamine; D007213:Indomethacin