Characterization of bradykinin receptors in peripheral organs.
Bradykinin (BK) and related kinins are potent stimulants of the rabbit jugular vein, the hamster urinary bladder, and the guinea pig trachea. The characterization of kinin receptors in these tissues was made with agonists and antagonists. Results obtained with agonists indicate that bradykinin and kallidin are much more active than des-Arg9-BK and suggest the presence of B2 receptors in the three organs. Some new agonists were also tested and the BK analogue, [Hyp3,Tyr(Me)8]BK, was found to be a potent and selective stimulant of the three preparations, with pD2 values of 8.56, 8.00, and 8.39, respectively, but inactive on the rabbit aorta (a B1-receptor system). Contractile effects of kinins in the rabbit jugular vein and hamster urinary bladder were reduced or eliminated by B2-receptor antagonists but at different concentration levels; e.g., acetyl-D-Arg[Hyp3,D-Phe7]BK showed pA2 values of 7.78 on the rabbit jugular vein but only 5.72 on hamster urinary bladder. This compound contracted the guinea-pig trachea and was found to be inactive as an antagonist on this preparation. Contractions of the hamster urinary bladder and the guinea-pig trachea in response to bradykinin were markedly reduced or eliminated by indomethacin and by BW 755C, while those of the rabbit jugular vein were not modified. The present findings indicate that the myotropic effect of kinins on the rabbit jugular vein depends on the activation of B2 receptors and suggest that B2 receptors are largely responsible also for the response of the hamster urinary bladder. B2 receptors and (or) a nonreceptor mechanism appear to be involved in the stimulant effects of the kinin agonists and some antagonists in the guinea-pig trachea.
Rhaleb
N E
NE
Department of Pharmacology, Faculty of Medicine, University of Sherbrook, Qué., Canada.
Rouissi
N
N
Drapeau
G
G
Jukic
D
D
Regoli
D
D
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006224:Cricetinae; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects; D020024:Leukotriene Antagonists; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D020024:Leukotriene Antagonists; D008688:Methacholine Compounds; D011448:Prostaglandin Antagonists; D011804:Quinolines; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C059177:SR 2640; D013373:Substance P; C013509:diphloretin phosphate; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015288:Neurokinin A; D011121:Polyphloretin Phosphate; D001920:Bradykinin; D007213:Indomethacin