Debeljuk L, Bandera R, Bartke A
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, USA.
J Physiol Pharmacol. 1997 Sep;48(3):461-78.
Tachykinins are present in the anterior pituitary gland and there is evidence that they may have a direct intrapituitary role influencing the secretion of some of the hormones released by this gland. In this investigation, we have studied the effect of the non-peptide NK-2 receptor antagonist SR 48,968 (Sanofi Recherche) on the basal release of LH, FSH, and prolactin by rat hemipituitaries incubated in vitro, and also on the response to GnRH. SR 48,968 significantly inhibited prolactin release into the medium. The highest doses of this compound stimulated the basal release of LH by hemipituitaries from castrated, castrated testosterone-treated, and ovariectomized estradiol-treated rats, but not from intact male rats. SR 48,968 significantly inhibited the release of LH in response to GnRH. Since some tachykinin receptor antagonists have been demonstrated to act also on calcium channels, studies with verapamil, a calcium channel antagonist, were also carried out for comparison. Verapamil inhibited prolactin release into the medium and decreased the LH response to GnRH. These results suggest that tachykinins that bind NK-2 receptors, may have an intrapituitary role stimulating the release of prolactin, and that they may also modulate the response of the gonadotrophs to GnRH. The fact that verapamil shares some of the actions exerted by NK-2 receptor antagonists on the pituitary glandm however, suggests the possibility that some of the effects of NK-2 receptor antagonists may be mediated through calcium channel antagonism. Therefore, the results observed with the use of some of these antagonists should be interpreted with great caution.
速激肽存在于垂体前叶，有证据表明它们可能在垂体内部发挥直接作用，影响该腺体释放的某些激素的分泌。在本研究中，我们研究了非肽类NK-2受体拮抗剂SR 48,968（赛诺菲研究公司）对体外培养的大鼠半垂体中促黄体生成素（LH）、促卵泡生成素（FSH）和催乳素基础释放的影响，以及对促性腺激素释放激素（GnRH）的反应。SR 48,968显著抑制催乳素释放到培养基中。该化合物的最高剂量刺激了去势、去势后用睾酮处理以及卵巢切除后用雌二醇处理的大鼠半垂体中LH的基础释放，但未刺激完整雄性大鼠半垂体中LH的基础释放。SR 48,968显著抑制了对GnRH反应时LH的释放。由于已证明一些速激肽受体拮抗剂也作用于钙通道，因此还进行了钙通道拮抗剂维拉帕米的研究以作比较。维拉帕米抑制催乳素释放到培养基中，并降低了LH对GnRH的反应。这些结果表明，与NK-2受体结合的速激肽可能在垂体内部发挥刺激催乳素释放的作用，并且它们还可能调节促性腺细胞对GnRH的反应。然而，维拉帕米具有NK-2受体拮抗剂对垂体所发挥的一些作用这一事实表明，NK-2受体拮抗剂的某些作用可能是通过钙通道拮抗作用介导的。因此，使用这些拮抗剂中的一些所观察到的结果应谨慎解释。
