Contractile effects of bradykinin on the isolated human small bronchus.
Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.
Molimard
M
M
Laboratoire de Pharmacologie, Faculté de Médecine Paris Ouest, France.
Martin
C A
CA
Naline
E
E
Hirsch
A
A
Advenier
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D018002:Receptors, Bradykinin / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D001549:Benzamides; D001713:Biphenyl Compounds; D010880:Piperidines; D018002:Receptors, Bradykinin; D012430:Ruthenium Red; C072121:bradykinin, Sar-(D-Phe(8))des-Arg(9); D013779:Tetrodotoxin; C051090:bradykinin, Leu(8)-des-Arg(9)-; C073839:SR 48968; D001285:Atropine; C065679:icatibant; D015288:Neurokinin A; D000109:Acetylcholine; D002211:Capsaicin; D001920:Bradykinin; C066892:CP 96345; D007213:Indomethacin