Intrastriatal injection of endothelin evokes dopaminergic turning behaviour in rats through activation of the ETB receptor.
Contralateral intrastriatal injection of 0.1 pmol or 1 pmol of endothelin-1 produced ipsilateral turning behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway. This effect could be abolished by pretreatment with either the endothelin ETA/B receptor antagonist bosentan (1 nmol, intrastriatally) or the dopamine D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) suggesting that endothelin is acting at endothelin receptors to evoke ipsilateral turning behaviour and that this response is mediated by dopamine. Similar ipsilateral turning behaviour was observed upon intrastriatal injection of 1 pmol of endothelin-3 or the specific ETB receptor agonist, [Ala1,3,11,15]endothelin-1 when compared to endothelin-1. Pretreatment with the specific ETB receptor antagonist BQ788 blocked the ipsilateral turning response to intrastriatal injection of endothelin-1 while pretreatment with the specific ETA receptor antagonist BQ123 did not significantly change the response to injection of endothelin-1. This indicates that endothelin-1, which has affinity for both ETA and ETB receptors, is most likely acting at the ETB receptor to elicit its effect. These results suggest that low doses of endothelin may act at ETB receptors to evoke the release of dopamine from the striatum in vivo.
Webber
K M
KM
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Vic., Australia.
van den Buuse
M
M
D000818:Animals; D000077300:Bosentan; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D008297:Male; D017072:Neostriatum / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013565:Sympatholytics / Q000633:toxicity
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; D013449:Sulfonamides; D013565:Sympatholytics; C086539:BQ 788; D016627:Oxidopamine; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D004298:Dopamine