Facilitatory effects of pituitary adenylate cyclase activating polypeptide (PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus (PVN) in vitro.

To establish the role of pituitary adenylate cyclase activating polypeptide (PACAP), a member of vasoactive intestinal polypeptide (VIP) family, as a neurotransmitter/neuromodulator in the central nervous system, the effects of PACAP38, PACAP27 and VIP on the single neuron activity in the magnocellular portion of the hypothalamic paraventricular nucleus (mg.PVN) were examined in rat brain slice preparations. Extracellular recordings were made from 111 neurons in the mg.PVN, which fired spontaneously at an average rate of 1.85 +/- 0.2 spikes/s (mean +/- SEM). PACAP38 and PACAP27 were applied to 78 and 33 of the 111 neurons, respectively. Perfusion with PACAP38 in doses between 10 nM and 1 microM increased the firing rate of 56 (71.8%) of the 78 neurons in a dose-dependent manner. The threshold dose of PACAP38 to excite the neurons seemed to lie below 10 nM. The application of PACAP27 (1 microM) also increased the firing rate of 19 (57.6%) of the 33 neurons tested. Eleven (52.4%) of 21 neurons which were excited by PACAP38 also showed excitation following perfusion with VIP (1 microM). The responses to PACAP38 in 12 of 20 neurons and those to VIP in 6 of 9 neurons tested were still observed in a low Ca2+ and high Mg2+ medium. Although there was no difference in the mean latency between the responses to PACAP38 (1 microM) and VIP (1 microM) (2.1 +/- 0.1 min and 2.4 +/- 0.4 min, respectively), the duration of the PACAP38-induced excitation (59.0 +/- 5.0 min) was much longer than that of the VIP-induced one (18.8 +/- 3.1 min). The PACAP38 (30 nM)-induced excitation was reversibly blocked by a concurrent application of PACAP5-38 (300 nM), a PACAP receptor antagonist. While a selective VIP receptor antagonist, [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (1 microM), did not affect the excitatory responses to PACAP38 (300 nM), it completely blocked the VIP (1 microM)-induced excitation. These findings suggest that PACAP may therefore modulate the secretion of the pituitary hormones at least partly by its action on the neurons in the mg.PVN through the activation of specific receptors for PACAP.