Parasympathetic neurotransmission in rabbit isolated bronchus is modulated at prejunctional sites via endothelinB receptor stimulation.
OBJECTIVE
The aim of this study was to investigate the mechanism involved in endothelin-induced potentiation of the response to parasympathetic nerve stimulation.


METHODS
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.
McKay
K O
KO
Department of Pharmacology, The University of Sydney, New South Wales, Australia. karenm8@nch.edu.au
Johnson
P R
PR
Black
J L
JL
Armour
C L
CL
D000818:Animals; D001345:Autoradiography; D001980:Bronchi / Q000502:physiology*; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D019334:Endothelin-3 / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019334:Endothelin-3; D009842:Oligopeptides; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D017981:Receptors, Neurotransmitter; D014757:Viper Venoms; C057354:sarafotoxins s6; C082887:PD 145065; C072247:cyclo(Trp-Asp-Pro-Val-Leu)