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  • Title: Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, an endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin-B receptor agonist.
    Author: Yamamoto T, Shimoyama N, Asano H, Mizuguchi T.
    Journal: J Pharmacol Exp Ther; 1994 Oct; 271(1):156-63. PubMed ID: 7965709.
    Abstract:
    Endothelin (ET)-A and ET-B receptors have been reported to exist in the spinal cord but the roles of ET-A and ET-B receptors in the spinal cord are poorly understood. To gain a better understanding of the roles of ET-A and ET-B receptors in nociceptive information transmission in the spinal cord, this study evaluated the effects of ET-1, ET-3, Sarafotoxin S6c (an ET-B receptor-selective agonist) and (R)2-[(R)-2-[(S)-2-[[1- (hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3- [3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyridyl)propionic acid (FR139317, an ET-A receptor-selective antagonist) on the agitation behavior evoked by formaldehyde solution injection and on the thermal nociceptive test. The s.c. injection of formaldehyde solution into the hind paw evoked a biphasic flinching (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For the purpose of data analysis, phase 2 was further divided into two phases (phase 2a, 10-34 min; phase 2b, 35-60 min). Intrathecal injection of ET-1 depressed the phase 1 and 2 flinching behavior in a dose-dependent manner and this ET-1 effect was antagonized by FR139317. Intrathecal injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a flinching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on the thermal nociceptive test. These data indicate that ET-A and ET-B receptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal stimulation.
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