Effect of N-formyl-L-methionyl-L-leucyl-L-phenylalanine and its analogues on blood pressure.

Saito, Haruo; Matsuo, Motoya; Naminohira, Shigeru; Sakai, Takeshi; Kitagawa, Haruo; Hirata, Arthur A.

doi:10.1248/bpb1978.6.141

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…It is perhaps not fully appreciated that both chemotactic peptides elicit remarkable effects on the circulation in vivo, particu larly in rabbits [4][5][6][7] and also in several iso lated vascular smooth muscle preparations incubated in blood-free physiological media. The vasomotor effect of both types of che motactic peptides has been described in iso lated vascular strips or rings from several animal species [4,[8][9][10], Relaxation is the dominant response to either purified human C5a or to FMLP (1-100 nM ) in rabbit vas cular strips obtained from the portal vein or the pulmonary artery [4,8,11 ].…”

Section: Introductionmentioning

confidence: 99%

Relaxant Effect of Chemotactic Peptides on Rabbit Vascular Strips: Evidence for Nitric Oxide Release from a Nonendothelial Source

Petitclerc

Marceau²

1991

J Vasc Res

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Two distinct peptides, C5a and f-Met-Leu-Phe (FMLP), that are chemotactic for phagocytic leukocytes affect profoundly the circulation in various in vivo systems. These peptides are known to relax strips of rabbit isolated blood vessels, the portal vein and pulmonary artery. In the present study, the effect of recombinant human C5a (2.5–25 nM) was examined and found to be qualitatively similar to that previously reported for FMLP. Indomethacin completely or partially inhibited the vasorelaxations induced by either peptide in the pulmonary artery and the portal vein, respectively. The relaxation induced by C5a was not abolished by removing the endothelial lining of the model vessels. The C5a or FMLP effects were more tachyphylactic in tissues continuously exposed to cycloheximide; this phenomenon was particularly pronounced for FMLP. A series of experiments were focused on the indomethacin-resistant component of the relaxation induced by either peptide on the portal vein. This component was not inhibited by capsaicin pretreatment or by endothelium removal, but was suppressed by treatment with N^G-nitro-L-arginine or reduced by LY-83583. These findings suggest that the chemotactic peptides elicit their mechanical effect on rabbit vascular smooth muscle through the release of secondary mediators not related to the endothelium; the mediators are tentatively identified as prostaglandins and nitric oxide. It is the coordinated combinations of the metabolic pathways that are involved in the final responses, with inherent differences between vessel sources and the agonists used.

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Section: Introductionmentioning

confidence: 99%

Relaxant Effect of Chemotactic Peptides on Rabbit Vascular Strips: Evidence for Nitric Oxide Release from a Nonendothelial Source

Petitclerc

Marceau²

1991

J Vasc Res

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The influence of prostaglandins on leukocyte-endothelium interactions in rabbit mesenteric venules

Tromp

Tangelder

Slaaf

et al. 2000

Prostaglandins & Other Lipid Mediators

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Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

Berend¹,

Peters²,

Armour³

et al. 1988

Thorax

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Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV, 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of > 20% in FEV, (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0-06, 0-12, 025, 0-5, 1-0, 2-0, and 4-0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV, being recorded after inhalation ofeach concentration. Dose dependent falls in FEV, occurred in five non-smokers (geometric mean 1 76, 95% confidence limits 0-87-3-53 mg/ml) and three smokers (0-23, 0O07-0 78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 ,ug of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.Bacteria elaborate chemotactic factors for leucocytes.'-3 These factors have been isolated and characterised as small molecular weight peptides."5 In subsequent studies of the structure-activity relations of synthetic chemotactic peptides6 the acylated tripeptide formyl-methionyl-leucyl-phenylalanine (FMLP) was shown to be the most active chemotactic agent.With an ED_, for rabbit neutrophil chemotaxis of 70 pmol/l, FMLP is one of the most potent chemotaxins known. The well defined chemical structure of the ligand has permitted detailed studies of the nature of the receptor that is present on macrophages and

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Effect of N-formyl-L-methionyl-L-leucyl-L-phenylalanine and its analogues on blood pressure.

Cited by 3 publications

References 4 publications

Relaxant Effect of Chemotactic Peptides on Rabbit Vascular Strips: Evidence for Nitric Oxide Release from a Nonendothelial Source

Relaxant Effect of Chemotactic Peptides on Rabbit Vascular Strips: Evidence for Nitric Oxide Release from a Nonendothelial Source

The influence of prostaglandins on leukocyte-endothelium interactions in rabbit mesenteric venules

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

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