Broqua P, Laude D, Bluet-Pajot M T, Schmidt B, Baudrie V, Chaouloff F
Laboratoire de Pharmacologie, CNRS, CHU Necker-EM, Paris, France.
Neuroendocrinology. 1993 Apr;57(4):640-7. doi: 10.1159/000126419.
Administration of the serotonin (5-HT)1A receptor agonist ipsapirone has been shown to decrease cold-elicited thyrotropin (TSH) secretion. We have analyzed (1) the influence of 5-HT1A receptors and ipsapirone metabolism into 1-(2-pyrimidinyl)-piperazine (1-PP, an alpha 2-adrenoceptor antagonist) on the effect of ipsapirone on TSH release, and (2) the interaction between the corticosterone-releasing effect of ipsapirone and its inhibitory influence on TSH release. Pretreatment with proadifen (50 mg/kg, 5 h before ipsapirone), i.e. an inhibitor of ipsapirone metabolism into 1-PP, did not affect ipsapirone-induced inhibition of cold-elicited TSH secretion. Pretreatment (15 min before ipsapirone) with the 5-HT1/5-HT2 receptor antagonist metergoline 2 mg/kg) or with the 5-HT1A receptor blocker (-)-pindolol (5 mg/kg) increased baseline and cold-elicited TSH release but the inhibitory influence of ipsapirone on cold-elicited TSH release was alleviated by (-)-pindolol pretreatment only. Cold exposure increased corticosterone release, an effect which was insensitive to (-)-pindolol pretreatment. Lastly, pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine prevented the immediate inhibitory effect of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) upon cold-induced TSH release, but it amplified the late release of TSH in cold-exposed 8-OH-DPAT-injected rats. These results suggest that presynaptic 5-HT1A receptors mediate ipsapirone-induced inhibition of cold-elicited TSH release, an effect which may be partially opposed by postsynaptic 5-HT1A receptor stimulation.
血清素（5-羟色胺，5-HT）1A受体激动剂伊沙匹隆的给药已被证明可减少寒冷诱发的促甲状腺激素（TSH）分泌。我们分析了：（1）5-HT1A受体以及伊沙匹隆代谢为1-（2-嘧啶基）-哌嗪（1-PP，一种α2-肾上腺素能受体拮抗剂）对伊沙匹隆影响TSH释放的作用；（2）伊沙匹隆的促肾上腺皮质激素释放作用与其对TSH释放的抑制作用之间的相互作用。用丙胺太林（50mg/kg，在给予伊沙匹隆前5小时）预处理，即伊沙匹隆代谢为1-PP的抑制剂，并不影响伊沙匹隆诱导的对寒冷诱发的TSH分泌的抑制作用。用5-HT1/5-HT2受体拮抗剂美替拉酮（2mg/kg）或5-HT1A受体阻滞剂（-）-吲哚洛尔（5mg/kg）在（给予伊沙匹隆前15分钟）预处理可增加基础和寒冷诱发的TSH释放，但只有（-）-吲哚洛尔预处理可减轻伊沙匹隆对寒冷诱发的TSH释放的抑制作用。冷暴露可增加皮质酮释放，该作用对（-）-吲哚洛尔预处理不敏感。最后，用5-HT合成抑制剂对氯苯丙氨酸预处理可阻止选择性5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）对寒冷诱导的TSH释放的即时抑制作用，但它可放大注射8-OH-DPAT的冷暴露大鼠中TSH的后期释放。这些结果表明，突触前5-HT1A受体介导伊沙匹隆诱导的对寒冷诱发的TSH释放的抑制作用，该作用可能部分被突触后5-HT1A受体刺激所抵消。
