title: FMLP actions and its binding sites in isolated human coronary arteries.
abstract: The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial tone without the involvement of peripheral leukocytes. We investigated the actions of FMLP and its cellular mechanism in human coronary arteries isolated 2-3 h after death. A single dose of FMLP (0.01-10 microM) produced transient contraction (or, followed by relaxation) responses in most human coronary rings examined. These responses to FMLP were in large part mediated by the generation of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Radiolabeled N-formyl hexapeptide. 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound densely to intimal and adventitial sites that accumulated macrophages (CD68-positive) with a Kd of 14-29 nM and, further, weakly to the media with a Kd of 2.4-3.6 microM. Several cell types including macrophages, endothelial cells and smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2 synthase. However, there was no significant relation between the magnitude of the responses to FMLP and dense macrophage accumulation in the intimal plaques or the adventitia. A reverse transcription-polymerase chain reaction showed predominant expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary medial tissues relative to that in leukocytes. In conclusion. FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the activation of densely accumulated intimal and/or adventitial macrophages, but by the activation of unidentified medial tissue cells which might have functional FMLP receptor homologues.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Keitoku
authors.forename: M
authors.initials: M
authors.lastname: Kohzuki
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Funakoshi
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: A
authors.initials: A
authors.lastname: Karibe
authors.forename: S
authors.initials: S
authors.lastname: Horiguchi
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Nose
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Okayama
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000032:analysis; D007537:Isometric Contraction / Q000187:drug effects*; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D011453:Prostaglandins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics; D018000:Receptors, Peptide / Q000032:analysis* / Q000235:genetics; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009842:Oligopeptides; D011453:Prostaglandins; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013764:Tetrahydronaphthalenes; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; C021642:F-chemotactic peptide; C049855:ONO 3708; D003577:Cytochrome P-450 Enzyme System; C056295:nafagrel; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase; D007213:Indomethacin