Selective and non-selective ET antagonists reveal an ET(A)/ET(B) receptor mediated ET-1-induced antinociceptive effect in PAG area of mice.
The injection of endothelin-1 (ET-1) (2 pmol) into the dorsolateral periaqueductal gray area (PAG) of mice produces antinociceptive effect as underscored by increases in the latency time for the reaction to a hot plate. Pretreatment of the PAG area with bosentan (10 nmol) (a mixed ET(A)/ET(B) receptor antagonist), FR 139317 (5 nmol) (ET[A] receptor selective antagonist) or BQ-788 (5 nmol) (ET[B] receptor selective antagonist) greatly reduced the antinociceptive effect induced by ET-1. Therefore, ET-1 induces antinociceptive effects via both ET(A)/ET(B) receptors. In addition, since ET-antagonists lowered per se the control reaction time of the mice when administered alone to the PAG area, we would suggest that endogenous ET-1 acting within the PAG area contributes to the suppression of pain.
D'Amico
M
M
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, II University of Naples, Italy.
Di Filippo
C
C
Rossi
F
F
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D000700:Analgesics; D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; C079574:FR 139317; D000077300:Bosentan