Relaxant effect of N-formyl-methionyl-leucyl-phenylalanine on rabbit vascular strips.
Some types of rabbit isolated blood vessels precontracted with phenylephrine relaxed when exposed to the chemotactic peptide N-formyl-Met-Leu-Phe (FMLP). The thoracic aorta was unresponsive whereas the portal vein and pulmonary artery exhibited concentration-dependent relaxing responses to FMLP (1-100 nM). FMLP-induced relaxations developed over several minutes and occurred after a latency of 30 to 40 sec. An inconsistent, brief and small contractile phase preceded the relaxations in some tissues. Stable responses to FMLP could be obtained repeatedly at 1.5-hr intervals. On both the portal vein and the pulmonary artery, the structure-activity relationship of peptides related to FMLP was similar to the one reported for activating phagocytic leukocytes. The peptide Boc-Phe-D-Leu-Phe-D-Leu-Phe behaved as a competitive antagonist of FMLP-induced relaxations with a calculated pA2 of 7.5 on both types of responsive vessels. Indomethacin inhibited the relaxations completely on the pulmonary artery and partially on the portal vein. FMLP-induced vasorelaxations were unaffected by a platelet-activating factor antagonist, BN 52021, or a 5-lipoxygenase inhibitor, L-651,392. Removal of the endothelium did not prevent the relaxant response to FMLP. The release of 6-keto-prostaglandin F1 alpha in the bathing fluid of portal vein and pulmonary artery exposed to FMLP was demonstrated using a radioimmunoassay. FMLP relaxed rabbit vascular strips in a blood-free environment by releasing secondary mediators tentatively identified as prostaglandins; however, a component of the relaxation in the portal vein was not mediated by cyclooxygenase products.
Laplante
C
C
Unité de Recherche Inflammation et Immunologie-Rhumatologie, Centre Hospitalier de l'Université Laval, Québec, Canada.
Tremblay
B
B
Marceau
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003182:Complement C5 / Q000494:pharmacology; D015936:Complement C5a; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D003182:Complement C5; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D015121:6-Ketoprostaglandin F1 alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D000109:Acetylcholine