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The vasoactive intestinal peptide (VIP) has been located in various structures of the rat brain, but few actions of the peptide have been reported as yet. Because VIP might interact with classical neurotransmitter systems in the central nervous system as it does in the periphery, we investigated whether VIP can modulate serotonin (5- HT1) receptors in membrane preparations obtained from brain areas which contain various amounts of VIP and 5-HT receptors. The presence of bacitracin alone, which protects VIP from proteolytic degradation, decreases the affinity of [3H]5-HT binding in almost all of the structures tested. Scatchard analysis indicates that, in the presence of bacitracin, VIP significantly decreases the affinity and increases the number of specific high affinity binding sites for [3H]5-HT in the dorsal hippocampus. VIP induces a dose-dependent increase in the number of 5-HT1 receptors with a maximal response of 60% with 10(-7) M VIP. At the same concentration, neither secretin nor glucagon modifies 5-HT1 receptor density. No effect of VIP is observed in the ventral hippocampus, parietal cortex, whole hypothalamus, and midbrain. This effect of VIP is not observed when bacitracin is omitted, and the presence of calcium ions does not alter the efficacy of the VIP effect. No effect of VIP is obtained on [3H]spiperone binding assayed with 10 microM mianserin to define specific binding. The present data suggest that some of the effects of 5-HT in the hippocampus may be modulated by VIP.

Modulation by vasoactive intestinal peptide (VIP) of serotonin receptors in membranes from rat hippocampus