Ho B Y, Takemori A E
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis.
Eur J Pharmacol. 1990 Mar 27;178(3):371-3. doi: 10.1016/0014-2999(90)90117-o.
The antinociceptive action of s.c. administered U-50,488H was antagonized by s.c. administered ICS-205-930, a selective 5-HT3 receptor antagonist. To characterize the site of interaction, U-50,488H and ICS-205-930 were administered either intracerebroventricularly (i.c.v.) or intrathecally (i.t.). When U-50,488H was administered i.c.v., its antinociception action was antagonized by ICS-205-930 given either i.c.v. or i.t., increasing the ED50 values of U-50,488H by approximately twofold from 48 to 98 and 90 nmol/mouse, respectively. However, when U-50,488H was administered i.t., its antinociception action was not antagonized by ICS-205-930 given either i.c.v. or i.t. These findings suggest that i.c.v., but not i.t. administered U-50,488H may release serotonin both supraspinally and spinally to interact with 5-HT3 receptors to produce antinociception.
皮下注射U - 50,488H的抗伤害感受作用被皮下注射的ICS - 205 - 930（一种选择性5 - HT3受体拮抗剂）所拮抗。为了确定相互作用位点，将U - 50,488H和ICS - 205 - 930经脑室注射（i.c.v.）或鞘内注射（i.t.）。当经脑室注射U - 50,488H时，其抗伤害感受作用被经脑室或鞘内注射的ICS - 205 - 930所拮抗，使U - 50,488H的半数有效剂量（ED50）值分别从48 nmol/只小鼠增加到98 nmol/只小鼠和从48 nmol/只小鼠增加到90 nmol/只小鼠，约增加了两倍。然而，当经鞘内注射U - 50,488H时，其抗伤害感受作用未被经脑室或鞘内注射的ICS - 205 - 930所拮抗。这些发现表明，经脑室而非经鞘内注射的U - 50,488H可能在脊髓上和脊髓水平释放5 - 羟色胺，与5 - HT3受体相互作用以产生抗伤害感受。
