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Vascular mode of action of kinin B 1 receptors and development of a cellular model for the investigation of these receptors
Author(s) -
Levesque Luc,
Drapeau Guy,
Grose John H.,
Rioux Francis,
Marceau François
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13757.x
Subject(s) - kinin , bradykinin , prostacyclin , receptor , endocrinology , medicine , chemistry , stimulation , vascular smooth muscle , contraction (grammar) , prostaglandin , inositol , inositol phosphate , receptor antagonist , contractility , biology , antagonist , smooth muscle
1 Kinins exert a contractile effect on rabbit aortic rings via the stimulation of B 1 receptors. Des‐Arg 9 ‐bradykinin (BK) is more potent than BK on this receptor type. The mode of action of des‐Arg 9 ‐BK on rabbit aortic tissue has been studied by both the aortic ring contractility assay and a cellular model using cultured aortic smooth muscle cells (SMCs). 2 The des‐Arg 9 ‐BK‐induced contractions in rabbit aortic rings were unaffected by pretreatments with nifedipine, indomethacin, REV‐5901 (a 5‐lipoxygenase blocker) and LY‐83583 (a guanylyl cyclase inhibitor); however, the protein kinase inhibitors H‐7 and H‐9 significantly reduced the maximal effect of des‐Arg 9 ‐BK. 3 The contractile responses to des‐Arg 9 ‐BK in calcium‐free Krebs solution were slightly but not significantly attenuated in amplitude, as compared to paired control tissues bathed in Krebs solution, and sustained plateaus of contraction were observed in the absence of Ca 2+ . However, Ca 2+ replenishment further increased the kinin‐induced contraction measured in Ca 2+ ‐free bathing fluid. 4 Despite the lack of evidence of a mediating role for prostaglandin in the mechanical response to des‐Arg 9 ‐BK, the kinin stimulated the release of prostacyclin from rabbit aorta rings measured as immunoreactive 6‐keto‐prostaglandin F 1α (6‐keto‐PGF 1α ). 5 Smooth muscle cells (SMCs) derived from the rabbit aorta exhibit functional responses to des‐Arg 9 ‐BK in acute release of 6‐keto‐PGF 1α and of inositol phosphate turnover which were inhibited by pretreatment with the B 1 receptor antagonist, Lys[Leu 8 ]des‐Arg 9 ‐BK, but not by the B 2 receptor antagonist, Hoe‐140. Preincubation of the cells with interleukin‐1 (IL‐1) 20 h before stimulation with the kinin had no effect on basal inositol phosphate turnover, but potentiated the acute effect of des‐Arg 9 ‐BK. 6 These results suggest that second mesengers derived from the action of phospholipase C are produced by SMCs when B 1 receptors are activated in rabbit aortic tissue. Intracellular calcium stores are primarily mobilized by des‐Arg 9 ‐BK, although receptor‐controlled calcium influx has not been ruled out, and may contribute to initiate the contractile responses. The maintenance of the contractile state involves protein kinase C activity and is consistent with a current model of SMC function. The cell model retains some of the cardinal properties of B 1 receptor‐mediated vascular responses: endothelium‐independent PGI 2 release and up‐regulation by the cytokine IL‐1. PGI 2 is not involved in the mechanical response, possible because the rabbit aorta is refractory to this prostaglandin.