Bealer Steven L, Flynn Francis W
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112-5820, USA.
Exp Neurol. 2003 Dec;184(2):1027-33. doi: 10.1016/j.expneurol.2003.08.012.
Stimulation of central tachykinin receptors contributes to neuroendocrine functions of the hypothalamo-neurohypophyseal system. However, the specific role of each tachykinin receptor subtype has not been completely characterized. Specifically, while neurokinin 3 (NK3) receptor stimulation increases systemic vasopressin, the effects on oxytocin (OT) are not known. Therefore, the present studies investigated the effect of central NK3 receptor stimulation with senktide on release of systemic and central OT. Furthermore, since central NK3 receptors activate noradrenergic systems, which contribute to OT release, the effects of alpha-adrenergic receptor blockade on senktide-induced changes in OT release were evaluated. Female rats were implanted with a cannula in the third cerebral ventricle, and changes in plasma OT concentration determined before and following central administration of senktide in vehicle-treated rats, and animals following central administration of the alpha-adrenergic antagonist phentolamine. Other rats were implanted with microdialysis probes adjacent to the paraventricular nucleus (PVN), and dialysate and plasma OT concentrations were determined before and during administration of senktide through the dialysis probe. Central senktide increased systemic OT release, which was prevented by pretreatment with phentolamine. Furthermore, there was no detectable change in extracellular OT concentration in the PVN during dialysis administration of senktide. These data demonstrate that activation of central NK3 receptors stimulates systemic release of OT by activation of central noradrenergic systems, apparently without increasing intranuclear OT release in the PVN.
中枢速激肽受体的刺激作用有助于下丘脑 - 神经垂体系统的神经内分泌功能。然而，每种速激肽受体亚型的具体作用尚未完全明确。具体而言，虽然神经激肽3（NK3）受体的刺激会增加全身血管加压素，但对催产素（OT）的影响尚不清楚。因此，本研究探讨了用森克肽中枢刺激NK3受体对全身和中枢OT释放的影响。此外，由于中枢NK3受体激活去甲肾上腺素能系统，而去甲肾上腺素能系统有助于OT释放，因此评估了α - 肾上腺素能受体阻断对森克肽诱导的OT释放变化的影响。给雌性大鼠在第三脑室植入套管，在给予载体处理的大鼠中枢注射森克肽之前和之后，以及给予α - 肾上腺素能拮抗剂酚妥拉明后，测定血浆OT浓度的变化。其他大鼠在室旁核（PVN）附近植入微透析探针，并在通过透析探针给予森克肽之前和期间测定透析液和血浆OT浓度。中枢注射森克肽增加了全身OT释放，酚妥拉明预处理可阻止这种增加。此外，在透析给予森克肽期间，PVN中细胞外OT浓度没有可检测到的变化。这些数据表明，中枢NK3受体的激活通过激活中枢去甲肾上腺素能系统刺激全身OT释放，显然不会增加PVN中核内OT释放。
