Pharmacologic analysis of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine-induced increases in cutaneous vascular permeability in the rat.
1-0-Alkyl-2-Acetyl-sn-Glycero-3-Phosphocholine (AGEPC) produced dose-dependent (75-500 ng/site) increases in cutaneous vascular permeability (CVP) in rats as measured by extravasation of Evans blue dye. In contrast, lyso-AGEPC, at 1000 ng/site, was without effect. Pyrilamine, methysergide, and phenoxybenzamine, antagonists of mast-cell derived mediators, did not affect the AGEPC-induced increase in CVP. Likewise, agents capable of inhibiting mast cell mediator release, such as disodium cromoglycate, PRD-92-EA, theophylline, or nifedipine, had no effect. The cyclooxygenase inhibitor indomethacin produced significant inhibition of the response to AGEPC, whereas the lipoxygenase inhibitor nordihydroguiaretic acid (NDGA) and the peptide leukotriene antagonist FPL 55712 were without effect. The response to AGEPC was enhanced by the vasodilator PGE2 and inhibited by the vasoconstrictor phenylephrine. The selective AGEPC antagonist CV-3988 provided marked inhibition of the response. Unaccountably, the combination of indomethacin and CV-3988 provided no greater inhibition of the responses than either agent alone. These observations indicate that the AGEPC-induced increase in CVP in rats is mediated in part by products of the cyclooxygenase pathway and in part by activation of an AGEPC receptor.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D002867:Chromones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; D010643:Phenoxybenzamine; D009637:Masoprocol; C037913:CV 3988; C006312:FPL 55712; D013806:Theophylline; D011738:Pyrilamine; D009543:Nifedipine; D007213:Indomethacin; D008784:Methysergide