Vascular actions of thrombin receptor peptide.
We have examined the action of the thrombin receptor-derived polypeptide, S42FLLRNPNDKYEPF55 (TRP 42-55), in rat and guinea pig aortic rings and helical arterial strips, and we have compared the actions of the peptide with those of thrombin. In rat preparations, both TRP 42-55 and thrombin caused a concentration-dependent endothelium-dependent relaxation that was blocked by N omega-nitro-L-arginine methyl ester; the relaxation response of the intact rat aortic strip preparation to concentrations of the peptide in the range 30-60 micrograms/mL (17-34 microM) was equivalent to the response to 0.03-0.1 U/mL of thrombin (about 0.3-0.9 nM), yielding a potency ratio (TRP 42-55:thrombin) of about 38,000:1. In contrast with the complete desensitization of thrombin-treated rat aortic preparations to a second administration of the enzyme, the rat aortic tissue was not desensitized by repeated exposures to TRP 42-55 and remained responsive to the peptide even after treatment of the tissue by thrombin. In contrast with the rat aortic tissue, in either intact or endothelium-free guinea pig aortic preparations both TRP 42-55 and thrombin caused a concentration-dependent endothelium-independent contraction. The contractile action of 60 micrograms/mL of receptor peptide (34 microM) in guinea pig aortic strip preparations was equivalent to the contractile action of 0.1-0.3 U/mL thrombin (0.9-3 nM), yielding a potency ratio of about 17,000:1. In guinea pig aortic preparations with an intact endothelium that were precontracted with noradrenaline, neither thrombin nor TRP42-55 caused relaxation, whereas substance P did so.(ABSTRACT TRUNCATED AT 250 WORDS)
Muramatsu
I
I
Department of Pharmacology, Fukui Medical School, Japan.
Laniyonu
A
A
Moore
G J
GJ
Hollenberg
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D007202:Indicators and Reagents; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D007202:Indicators and Reagents; D010446:Peptide Fragments; D010455:Peptides; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; C072032:thrombin receptor peptide (42-55); D001120:Arginine; D013917:Thrombin; D019331:NG-Nitroarginine Methyl Ester