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Parasympathetic neurotransmission in rabbit isolated bronchus is modulated at prejunctional sites via endothelin B receptor stimulation
Author(s) -
McKay Karen O.,
Johnson Peter R. A.,
Black Judith L.,
Armour Carol L.
Publication year - 2000
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2000.00274.x
Subject(s) - long term potentiation , endocrinology , medicine , endothelin receptor , agonist , receptor antagonist , stimulation , hexamethonium , receptor , phentolamine , endothelins , antagonist , pharmacology
Objective: The aim of this study was to investigate the mechanism involved in endothelin‐induced potentiation of the response to parasympathetic nerve stimulation. Methodology: We used autoradiographic and functional studies in rabbit isolated bronchi. Results: Autoradiography revealed dense binding sites for radiolabelled endothelin‐3 over bronchial parasympathetic ganglia. The contractile response of the bronchus to electrical field stimulation was significantly potentiated by endothelin‐3, endothelin‐1, sarafotoxin S6c and BQ‐3020 to 326 ± 53%, 293 ± 63%, 514 ± 119% and 655 ± 178%, respectively, of control values. The endothelin‐3‐induced potentiation of neurally evoked responses was not affected by the presence of propranolol, phentolamine or hexamethonium. The potentiation was also unaltered by pretreatment with the endothelin A receptor antagonist BQ‐123 (3 μmol/L), but was significantly reduced in the presence of the combined endothelin A /endothelin B receptor antagonist PD 145065, indicating that the potentiation was mediated via endothelin B receptors. Confirmation of endothelin B receptor involvement in the neuropotentiation was obtained by demonstration of a significant amelioration of the potentiation in the presence of the endothelin B receptor selective antagonist BQ‐788, and after endothelin B receptor desensitization by the endothelin B receptor selective agonist sarafotoxin S6b. Conclusions: These results suggest that the endothelin‐induced potentiation of parasympathetic neural responses in the rabbit bronchus is mediated via endothelin B receptor activation.