Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro.
1. The in vitro motor function of protease-activated recepter-1 (PAR-1), PAR-2 and PAR-4 and the presence by immunohistochemistry of PAR-1 in the human renal artery have been investigated. 2. Thrombin and the human PAR-1 (SFLLRN-NH(2)) activating peptide, but not the PAR-1 reverse peptide (NRLLFS-NH(2)), contracted both endothelial-intact and endothelial-denuded human renal artery strips, whereas no relaxation was observed either in strips non-precontracted or precontracted with phenylephrine. Maximum contraction by thrombin or SFLLRN-NH(2) was about 60% of phenylephrine. However, thrombin was approximately 1000-fold more potent than SFLLRN-NH(2). 3. PAR-1 desensitisation, using repeated applications of SFLLRN-NH(2), almost completely blocked the response to thrombin. The contractile effect produced by thrombin and SFLLRN-NH(2) was not affected by nitric oxide synthase inhibition, but was significantly reduced by cyclooxygenase blockade. 4. Trypsin, the PAR-2 (SLIGKV-NH(2) and SLIGRL-NH(2)) and PAR-4 (GYPGQV-NH(2) and AYPGKF-NH(2)) activating peptides did not produce any significant contraction or relaxation. 5. In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR-1 in the human renal artery. 6. Combined, these studies would suggest a possible role for PAR-1 in renal vascular homeostasis.
Department of Experimental and Clinical Medicine, Pharmacology Unit, University of Ferrara, S. Anna Hospital, Via Fossato di Mortara 19, 44100 Ferrara, Italy.
Michele
M
Tognetto
Michael R
MR
D'Andrea
Marcello
M
Trevisani
Remo
R
Guerrini
Severo
S
Salvadori
Lorella
L
Spisani
Carlo
C
Daniele
Patricia
P
Andrade-Gordon
Pierangelo
P
Geppetti
Selena
S
Harrison
D046508:Culture Techniques; D006801:Humans; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D044464:Receptor, PAR-2 / Q000819:agonists; D018179:Receptors, Thrombin / Q000819:agonists; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009842:Oligopeptides; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D013917:Thrombin; C112908:protease-activated receptor 4