Gozes I, Meltzer E, Rubinrout S, Brenneman D E, Fridkin M
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Endocrinology. 1989 Dec;125(6):2945-9. doi: 10.1210/endo-125-6-2945.
Vasoactive intestinal peptide (VIP) has been suggested as a neurotransmitter mediating penile erection. We now show that VIP can stimulate sexual behavior in rats with reduced masculine potential due to pituitary grafting or castration. This effect was attenuated in the presence of a novel VIP antagonist, devised by a hybrid peptide strategy. Thus, we have synthesized a molecule combining a portion of VIP with a portion of neurotensin, peptides of opposite pharmacological action on cAMP formation and smooth muscle relaxation. The hybrid peptide markedly inhibited VIP's effect on sexual behavior. This inhibition was manifested by a significant increase in the mean interval between copulatory events (greater than 3-fold change) coupled with a blockade of VIP-stimulated ejaculation. Other putative VIP antagonists were not as effective in blocking these activities. Thus, our results imply that VIP is not only associated with penile erection, but is involved in sexual behavior as well. Furthermore, the hybrid antagonist was shown to inhibit VIP binding in glial cell cultures. The availability of highly potent VIP antagonists may offer a route to study the possible multiple VIP receptors as well as help delineate other biological activities attributable to VIP.
血管活性肠肽（VIP）被认为是介导阴茎勃起的一种神经递质。我们现在表明，VIP能刺激因垂体移植或阉割而雄性潜能降低的大鼠的性行为。在一种通过杂合肽策略设计的新型VIP拮抗剂存在的情况下，这种效应会减弱。因此，我们合成了一种分子，它将VIP的一部分与神经降压素的一部分结合起来，这两种肽对环磷酸腺苷（cAMP）形成和平滑肌松弛具有相反的药理作用。这种杂合肽显著抑制了VIP对性行为的影响。这种抑制表现为交配事件之间的平均间隔显著增加（变化超过3倍），同时阻断了VIP刺激的射精。其他假定的VIP拮抗剂在阻断这些活动方面效果不佳。因此，我们的结果表明，VIP不仅与阴茎勃起有关，还参与性行为。此外，这种杂合拮抗剂被证明能抑制神经胶质细胞培养物中VIP的结合。高效VIP拮抗剂的可得性可能为研究可能的多种VIP受体提供一条途径，同时有助于阐明归因于VIP的其他生物学活性。
