Effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) on the spontaneous release of acetylcholine from the rat hippocampus by brain microdialysis.

Vasoactive intestinal polypeptide (VIP) has been suggested to have a presynaptic effect on cholinergic terminals in the rat hippocampus, which results in an activation of acetylcholine (ACh) synthesis. Recently, a VIP-related novel peptide, pituitary adenylate cyclase activating polypeptide (PACAP) was isolated from the ovine hypothalamus, and we previously demonstrated in the rat that PACAP binding site densities were high in the hippocampus. In the present study, we investigated the effects of VIP and PACAP on the release of ACh from the rat hippocampus. We succeeded in detecting the spontaneous release of ACh from the dorsal hippocampus in the conscious rat using microdialysis and HPLC-ECD. VIP, PACAP38 and PACAP27 were applied through a microinjection cannula placed in a region adjacent to the tip of a microdialysis tube. Injections of VIP, PACAP38 and PACAP27 (12, 120 pmol) resulted in dose-related increases in ACh release. The ability to enhance ACh release was VIP > PACAP38 > PACAP27. The increased release of ACh caused by these peptides was highly calcium-dependent. Tetrodotoxin (10(-6) M) added to the perfusion medium significantly reduced both the release of ACh enhanced by these peptides and the basal release. The present results suggest that VIP, PACAP38 and PACAP27 presynaptically stimulate cholinergic activity in the hippocampus, which may be reflected by an increase in ACh synthesis to maintain releasable terminal stores of ACh.