DEPRESSOR RESPONSES TO ENDOTHELIN-1 INTO THE SUPERIOR COLLICULUS OF RATS - PREDOMINANT ROLE OF ENDOTHELIN ETB RECEPTORS

We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the superficial gray layer of the superior colliculus o f rats. These studies showed dense binding of odotyrosyl(13))-[Ala(11, 15)]Ac-endothelin-1-(6-21) (BQ3020) (for endothelin ETB receptors), wh ile tissues incubated with xahydro-1-azepinyl)carbonyl)L-Leu(1-Me)D-Tr p-D-Tyr (PD151242) (for endothelin ET, receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonis ts, ( R)-2-[(R)-2-[(S)-2-[[1-hexahydro-1 no-4-methylpentanoyl]-amino-3 -(2-pyridyl)propionic acid (FR139317) (endothelin ETA receptor-selecti ve ), ( +)-(1 S,2 R,3 xy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl) -5 -(prop-1 -yloxy)indane-2-carboxylic acid (SB209670) (endothelin ETA /ETB receptor non-selective) and rbonyl-L-gamma-metLeu-D-1-methoxycarb onylTrp-D-Nle (BQ-788) (endothelin ETB receptor-selective antagonist) on the responses following administration of endothelin-1 into the sup erficial 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 wer e greatly reduced by pre-administration into the superior colliculus o f 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 sho wed that endothelin ET, receptors are the predominant mediators of dep ressor responses induced by endothelin-l injected into the superior co lliculus of the rat. (C) 1998 Elsevier Science B.V.