Influence of endothelin-1(1-31) on smooth muscle tone and cholinergic nerve-mediated contraction in rat isolated trachea.
Endothelin-1(1-21) (ET-1(1-21)) is a strong candidate as a significant mediator in asthma, in part because of its powerful spasmogenic actions and its ability to enhance cholinergic nerve-mediated contraction in human and animal airway smooth muscle. In the study reported here, we have demonstrated that [125I]ET-1(1-31) binds specifically to BQ-123-sensitive sites (presumably ET(A)-receptors) and to sarafotoxin S6c (S6c)-sensitive sites (presumably ET(B)-receptors) in rat tracheal and pulmonary airways, as well as in lung alveoli. These sites coexist in tracheal airway smooth muscle and in alveolar tissue in approximately equal proportions. ET-1(1-21) and ET-1(1-31) were equipotent and approximately equally active as spasmogens in rat tracheal smooth muscle. Importantly, both peptides were shown to potentiate cholinergic nerve-mediated rat tracheal contraction, although ET-1(1-31) was less active in this regard. These data are consistent with the idea that ET-1(1-31) could play a significant mediator role in obstructive airway diseases such as asthma.
Goldie
R G
RG
Department of Pharmacology, University of Western Australia, Nedlands, Australia. rgoldie@receptor.pharm.uwa.edu.au
D'Aprile
A C
AC
Self
G J
GJ
Rigby
P J
PJ
Henry
P J
PJ
D000818:Animals; D001345:Autoradiography; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D010446:Peptide Fragments