Receptor-activating peptides distinguish thrombin receptor (PAR-1) and protease activated receptor 2 (PAR-2) mediated hemodynamic responses in vivo.

Abstract

Vascular expression and cellular functions of the thrombin receptor (PAR-1) and protease activated receptor 2 (PAR-2) suggest similar but distinct vascular regulatory roles. The vascular actions of PAR-1 and PAR-2 in vivo were differentiated by monitoring mean arterial pressure (MAP) and heart rate (HR) of anesthetized mice in response to intravenous SFLLRN (0.1, 0.3, and 1 mumol/kg) and SLIGRL (0.1, 0.3, and 1 mumol/kg), the respective receptor-activating sequences for PAR-1 and PAR-2, and TFLLRNPNDK (0.3, 1, and 3 mumol/kg), a synthetic peptide selective for PAR-1. All peptides dose dependently decreased MAP (order of potency: SLIGRL > SFLLRN > TFLLRNPNDK). SLIGRL induced a more prolonged hypotension with a slow return to baseline, whereas SFLLRN- and TFLLRNPNDK-induced hypotension was followed by a rapid return towards baseline and a sustained moderate hypotension. SFLLRN and TFLLRNPNDK, but not SLIGRL, decreased HR. N omega-Nitro-L-arginine methyl ester HCl (L-NAME), an inhibitor of nitric oxide synthesis, attenuated the cumulative hypotensive response to SLIGRL but had no effect on the SFLLRN and TFLLRNPNDK hypotension. However, L-NAME revealed a rebound hypertension in response to SFLLRN and TFLLRNPNDK but not SLIGRL. In conclusion, activation of either PAR-1 or PAR-2 in vivo results in hypotension. In addition, only PAR-1 activation induced hypertension following L-NAME, reflecting concurrent PAR-1-mediated vasoconstriction. Thus, these different hemodynamic responses in vivo suggest distinct physiological or pathophysiological roles for PAR-1 and PAR-2 in local vascular regulation.

• Authors: W M Cheung, P Andrade-Gordon, C K Derian, B P Damiano
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 76 Issue 1 Pg. 16-25 (Jan 1998) ISSN: 0008-4212 [Print] Canada
• PMID: 9564545 (Publication Type: Journal Article)

Chemical References

• Oligopeptides
• Peptide Fragments
• Receptor, PAR-1
• Receptor, PAR-2
• Receptors, Thrombin
• seryl-leucyl-isoleucyl-glycyl-arginyl-leucine
• thrombin receptor peptide (42-47)
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Dose-Response Relationship, Drug
• Heart Rate (drug effects)
• Male
• Mice
• Oligopeptides (administration & dosage, pharmacology)
• Peptide Fragments (administration & dosage, pharmacology)
• Receptor, PAR-1
• Receptor, PAR-2
• Receptors, Thrombin (agonists)