Multiple mechanisms of bradykinin-induced contraction in rat and guinea pig smooth muscles in vitro.
Bradykinin caused graded contraction in the guinea pig ileum, trachea and urinary bladder and rat uterus and vas deferens in vitro. The order of potency (EC50, nM) was: ileum (3) > uterus (5) > trachea (15) > vas deferens (41) > urinary bladder (52) and the maximal responses (percentage to 80 mM KCl) were: 152 +/- 8 (ileum), 122 +/- 6 (uterus), 97 +/- 3 (urinary bladder), 75 +/- 5 (trachea) and 33 +/- 3 (vas deferens). Responses to bradykinin in guinea pig ileum and urinary bladder and rat vas deferens and uterus were markedly attenuated in Ca(2+)-free medium with or without EGTA or by nicardipine, whereas those in guinea pig trachea depended almost exclusively on intracellular Ca2+ sources which were sensitive to ryanodine. Treatment of the animals with pertussis toxin only inhibited bradykinin-induced contraction of the rat uterus. Furthermore, the protein kinase C inhibitors, H7 (5-isoquinolinysulfonyl-2-methyl-piperazine) and staurosporine, antagonized in a graded manner bradykinin responses in guinea pig ileum and trachea and rat vas deferens, indicating the possible dependence on activation of protein kinase C mechanisms, while responses of the rat uterus rely on coupling by a pertussis toxin-sensitive G protein. Thus, bradykinin acting at B2 receptors may induce contractions in several smooth muscles from rat and guinea pig through activation of multiple second messenger pathways.
Department of Pharmacology, Universidade Federal de Santa Catarina, SC, Brazil.
J B
JB
Calixto
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects; D014599:Uterus / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D001920:Bradykinin