Enkephalin heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe)-induced bronchospasm in guinea pigs: a non-naloxone reversible phenomenon.
Enkephalin heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MEAP ), is an enkephalin-related peptide derived from pre-pro-enkephalin A. Distribution studies have shown that MEAP is localized in the lung; in this organ there is very little Met-enkephalin (ME). To test the direct actions of MEAP in a tissue where it is differentially distributed from ME, MEAP was given intratracheally to anesthetized guinea pigs. MEAP produced a dose-related bronchospasm characterized by a slow onset (30-90 sec) and a duration exceeding 5 min. No significant effects on heart rate or blood pressure were observed concomitant with the pulmonary effects. ME or ethylketocyclazocine, tested at the same doses as MEAP , did not produce a bronchospasm. Moreover, naloxone failed to block MEAP 's effects. Therefore, it appears as if the MEAP -induced bronchospasm does not have an opioid-related mechanism of action. The bronchospasm produced by MEAP was not blocked by an anti-histamine (chlorpheniramine) or by vagotomy. However, inhibition of cyclo-oxygenase by ibuprofen blocked the MEAP -induced bronchospasm, suggesting that an arachidonic acid metabolite was involved in the effect. Blockade of MEAP 's pulmonary effects by an inhibitor of thromboxane synthetase (SQ 80338) and not by a leukotriene antagonist (FPL 55712) implied that MEAP 's mechanism of action may be via bronchospastic thromboxanes. These data are the first to demonstrate a non-opioid, thromboxane-mediated action of an enkephalin-related peptide.
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011312:Pressure; D014132:Trachea; D014628:Vagotomy
D002867:Chromones; D007093:Imidazoles; D009270:Naloxone; C025092:1-(3-phenyl-2-propenyl)-1H-imidazole; D004744:Enkephalin, Methionine; C027511:enkephalin-Met, Arg(6)-Phe(7)-; C006312:FPL 55712; D007052:Ibuprofen