Effects of capsaicin, (+/-)-CP-96,345 and SR 48968 on the bradykinin-induced airways microvascular leakage in guinea-pigs.
The aim of this study was to demonstrate the involvement of neuropeptides in the increase in microvascular permeability induced by bradykinin in guinea-pig airways in vivo and to determine the type of receptor involved. Extravasation of intravenously injected Evans blue dye was used as an index of vascular permeability. Increase in plasma exudation induced by bradykinin (0.3 micrograms/kg, iv) was reduced or abolished by capsaicin (40 mg/kg, sc, 7 days before experiments), a drug which destroys neurokinins in the NANC nerve endings. (+/-)-CP-96,345 (3 mg/kg, iv), an antagonist of neurokinin NK1-receptors, abolished the increase of vascular permeability induced by bradykinin and reduced or abolished the effects of substance P (0.3 micrograms/kg, iv). The higher dose of (+/-)-CP-96,345 (10 mg/kg, iv) completely blocked the effects of substance P, but it did not modify those of neurokinin A (100 micrograms/kg, iv). In contrast, SR 48968 (0.1 and 0.3 mg/kg, iv), an antagonist of neurokinin NK2-receptors, reduced the increase of vascular permeability induced by neurokinin A without influencing the effects of bradykinin and substance P. These results demonstrate that a stimulation of the non-adrenergic non-cholinergic (NANC) nerves and a subsequent release of neuropeptides, especially of substance P, is involved in the effects of bradykinin.
Qian
Y
Y
Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, France.
Emonds-Alt
X
X
Advenier
C
C
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D005070:Evans Blue; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D009411:Nerve Endings / Q000187:drug effects; D015288:Neurokinin A / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology
D001549:Benzamides; D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D013373:Substance P; D005070:Evans Blue; C073839:SR 48968; D015288:Neurokinin A; D002211:Capsaicin; D001920:Bradykinin; C066892:CP 96345