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Vasoactive Intestinal Peptide Potentiates Sexual Behavior: Inhibition by Novel Antagonist^*

ILLANA GOZES, EYAL MELTZER, SARA RUBINROUT, DOUGLAS E. BRENNEMAN and MATI FRIDKIN

Departments of Hormone Research Weizmann Institute of Science, Rehovot, Israel
Organic Chemistry Weizmann Institute of Science, Rehovot, Israel
the Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Illana Gozes, Building 36, Room 2A21, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

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 (> 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.

Footnotes

^* This work was supported in part by Fujimoto Pharmaceutical Corp. Patent is pending for the hybrid peptide antagonist for VIP.

On leave in the Laboratory of Developmental Neurobiology, NICHD, NIH. Incumbent of the Samuel 0. Freedman Career Development Chair established by the Montreal Chapter of the Canadian Society for the Weizmann Institute of Science.

Received June 7, 1989.

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