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  • Title: Depressor responses to endothelin-1 into the superior colliculus of rats: predominant role of endothelin ET(B) receptors.
    Author: D'Amico M, Di Filippo C, Rossi F.
    Journal: Eur J Pharmacol; 1998 Apr 17; 347(1):71-5. PubMed ID: 9650850.
    Abstract:
    We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the superficial gray layer of the superior colliculus of rats. These studies showed dense binding of (3-[125I]iodotyrosyl13)-[Ala11,15]Ac-endothelin-1-(6-2 1) (BQ3020) (for endothelin ETB receptors), while tissues incubated with [125I]( N-(hexahydro-1-azepinyl)carbonyl)L-Leu(1-Me)D-Trp-D-Tyr (PD151242) (for endothelin ETA receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonists, (R)-2-[(R)-2-[(S)-2-[[1-hexahydro-1H-azepinyl)]carbonyl]amino-4-++ +methylpentanoyl]-amino-3-(2-pyridyl)propionic acid (FR139317) (endothelin ETA receptor-selective), (+)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenediox yphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid (SB209670) (endothelin ETA/ETB receptor non-selective) and N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-metLeu-D-1-m ethoxycarbonylTrp-D-Nle (BQ-788) (endothelin ETB receptor-selective antagonist) on the responses following administration of endothelin-1 into the superficial layer of the superior colliculus. Endothelin-1 microinjected into this nucleus causes decreases in blood pressure (control, 109 +/- 6 mmHg, n = 6; endothelin-1, 72 +/- 5 mmHg, n = 6). These effects were greatly reduced by pre-administration into the superior colliculus of BQ-788 (5 nmol/rat) or SB209670 (3 nmol/rat) (94 +/- 5 and 98 +/- 6%, respectively) but were not affected by FR139317 (5 nmol/rat) (6 +/- 3%). Therefore, together with autoradiography, our functional data showed that endothelin ETB receptors are the predominant mediators of depressor responses induced by endothelin-1 injected into the superior colliculus of the rat.
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