Characterization of endothelin-induced nociception in mice: evidence for a mechanistically distinct analgesic model.
J Pharmacol Exp Ther
; 278(1): 1-7, 1996 Jul.
Article
en En
| MEDLINE
| ID: mdl-8764328
The behavioral response elicited in mice by an i.p. injection of endothelin-1 (ET-1) (0.1 mg/kg) was differentiated from that elicited by standard agents such as acetylcholine (ACh) (5.5 mg/kg) or phenyl-p-quinone (PpQ) (1.25 mg/kg). First, there was lack of two-way "cross-tolerance' between test paradigms. That is, at equieffective doses, a 60-min prior i.p. injection of ET-1 blocked the behavioral response to a subsequent i.p. injection of ET-1 or PpQ, but not of ACh, whereas a 60-min prior injection of ACh or of PpQ had no effect on a subsequent i.p. injection of ACh, PpQ or ET-1. Second, differential antagonism of ET-1-, ACh- or PpQ-induced responses was observed in an examination of 36 test compounds. For example, cyclo-oxygenase inhibitors such as indomethacin and ibuprofen did not block the ET-1-induced response at > 10 times the doses that blocked ACh- or PpQ-induced responses, whereas other compounds (such as certain benzodiazepines) inhibited ET-1-induced, but not ACh- or PpQ-induced, responses. These findings suggest that ET-1 produces a novel nociceptive stimulus, mechanistically distinct from ACh and PpQ. Hence, the ET-1-induced behavioral response in mice serves as a rapid and convenient measure of in vivo endothelin activity. In addition, this test might be a model for clinical pains not adequately treated by present analgesic agents or adequately tested by preclinical antinociceptive screens using ACh or PpQ. As such, it is a potentially valuable model for the identification of novel analgesic and other agents.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dimensión del Dolor
/
Endotelinas
/
Analgesia
/
Modelos Neurológicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos