Effect of bradykinin on airway neural responses in vitro.
We investigated the effects of bradykinin (BK) on airway excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic nerves in vitro. Neural responses were elicited by electrical field stimulation in guinea pig airways in vitro before and after the addition of BK (10(-10)-10(-7) M). Captopril (10(-5) M) and phosphoramidon (10(-6) M) were added to prevent degradation of BK, and all neural responses were measured in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M). BK potentiated e-NANC responses in bronchi in a concentration-dependent manner (10(-10)-10(-7) M) without changing concentration-response curves to exogenously applied substance P (10(-10)-10(-5) M). BK significantly potentiated e-NANC neural constrictor responses by 22 +/- 7% at 10(-8) M (mean +/- SE, n = 5, P < 0.05) and 32 +/- 7% at 10(-7) M (n = 8, P < 0.01), compared with changes in time-matched control tissues (7 +/- 2%, n = 8). The potentiation of e-NANC responses by BK was abolished by pretreatment with a specific B2-receptor antagonist, HOE 140 (10(-7) M). Cholinergic constrictor responses elicited to electrical field stimulation were not affected by the addition of BK (up to 10(-7) M). These results suggest that BK potentiates e-NANC bronchoconstrictor responses prejunctionally via a B2-receptor.
Miura
M
M
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Belvisi
M G
MG
Barnes
P J
PJ
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000031:analogs & derivatives; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D012137:Respiratory System / Q000187:drug effects / Q000294:innervation*; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D009842:Oligopeptides; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C065679:icatibant; D001920:Bradykinin