Cardiovascular responses mediated by protease-activated receptor-2 (PAR- 2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR- 2 or PAR-1

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	Cardiovascular responses mediated by protease-activated receptor-2 (PAR- 2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR- 2 or PAR-1
	Damiano B.P.1; Cheung W.-M.; Santulli R.J.; Fung-Leung W.-P.; Ngo K.; Ye R.D.2; Darrow A.L.; Derian C.K.; De Garavilla L.2; Andrade-Gordon P.
	1999-02-01
Source Publication	Journal of Pharmacology and Experimental Therapeutics
ISSN	00223565
Volume	288 Issue:2 Pages:671-678
Abstract	We developed mice deficient in protease-activated receptor-2 (PAR-2) or PAR-1 to explore the pathophysiological functions of these receptors. In this report, we evaluated mean arterial pressure and heart rate (HR) changes in response to PAR-1 or PAR-2 activation in anesthetized wild-type (WT), PAR-1- deficient (PAR-1(-/-)), and PAR-2-deficient (PAR-2(-/-)) mice. In WT mice, TFLLRNPNDK, a PAR-1 selective activating peptide, caused hypotension and HR decreases at 1 μmol/kg. TFLLRNPNDK also caused secondary hypertension following L-NAME pretreatment. These responses were absent in PAR-1(-/-) mice. In WT mice, SLIGRL, a PAR-2 selective activating peptide, caused hypotension without changing HR at 0.3 μmol/kg. SLIGRL did not induce hypertension following Nω-nitro-L-arginine-methyl ester-HCl (L-NAME). The response to SLIGRL was absent in PAR-2(-/-) mice. SFLLRN, a nonselective receptor activating peptide caused hypotension and HR decreases in WT mice at 0.3 μmol/kg, as well as secondary hypertension following L-NAME. SFLLRN still induced hypotension in PAR-1(-/-) mice, but HR decrease and secondary hypertension following L-NAME were absent. The hypotensive and bradycardic responses to SFLLRN and TFLLRNPNDK in PAR-2(-/-) mice were accentuated compared with WT mice. By using mouse strains deficient in either PAR-1 or PAR-2, we confirmed the in vivo specificity of TFLLRNPNDK and SLIGRL as respective activating peptides for PAR-1 and PAR-2, and the distinct hemodynamic responses mediated by activation of PAR-1 or PAR-2. Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk.
URL	View the original
Language	英語English
Fulltext Access	View Full-Text via Scopus
Document Type	Journal article
Collection	University of Macau
Affiliation	1.R. W. Johnson Pharmaceutical Research Institute 2.Scripps Research Institute
Recommended Citation GB/T 7714	Damiano B.P.,Cheung W.-M.,Santulli R.J.,et al. Cardiovascular responses mediated by protease-activated receptor-2 (PAR- 2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR- 2 or PAR-1[J]. Journal of Pharmacology and Experimental Therapeutics, 1999, 288(2), 671-678.
APA	Damiano B.P.., Cheung W.-M.., Santulli R.J.., Fung-Leung W.-P.., Ngo K.., Ye R.D.., Darrow A.L.., Derian C.K.., De Garavilla L.., & Andrade-Gordon P. (1999). Cardiovascular responses mediated by protease-activated receptor-2 (PAR- 2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR- 2 or PAR-1. Journal of Pharmacology and Experimental Therapeutics, 288(2), 671-678.
MLA	Damiano B.P.,et al."Cardiovascular responses mediated by protease-activated receptor-2 (PAR- 2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR- 2 or PAR-1".Journal of Pharmacology and Experimental Therapeutics 288.2(1999):671-678.

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