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Parasympathetic neurotransmission in rabbit isolated bronchus is modulated at prejunctional sites via endothelinB
K O McKay1, P R Johnson, J L Black
1Department of Pharmacology, The University of Sydney, New South Wales, Australia. karenm8@nch.edu.au
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 endothelinA receptor antagonist BQ-123 (3 micromol/L), but was significantly reduced in the presence of the combined endothelinA/endothelinB receptor antagonist PD 145065, indicating that the potentiation was mediated via endothelinB receptors. Confirmation of endothelinB receptor involvement in the neuropotentiation was obtained by demonstration of a significant amelioration of the potentiation in the presence of the endothelinB receptor selective antagonist BQ-788, and after endothelinB receptor desensitization by the endothelin, 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 endothelinB receptor activation.