Effects of PACAP, VIP and related peptides on cyclic AMP formation in rat neuronal and astrocyte cultures and cerebral cortical slices.

The effects of pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), peptide histidine-isoleucine (PHI) and peptide histidine-methionine (PHM) on cyclic AMP formation were studied in parallel on rat cerebral cortical slices, primary neuronal cultures and primary glial (astrocyte) cultures. PACAPappeared to be the most potent agent in all biological systems. The rank order of the peptides' potency was as follows: PACAP > VIP > PHI = PHM for cortical slices and neuronal cell cultures, and PACAP >> PHM approximately VIP > PHI for glial cell cultures. The cyclic AMP responses to the tested peptides, especially to PACAP, were distinctly larger in glial cell cultures than in neuronal cell cultures or brain slices. In an additional study, the cyclic AMP response to helodermin and secretin, as well as isoprenaline, histamine and forskolin, were tested in parallel on glial and neuronal cell cultures, and directly compared with the actions of PACAP. Helodermin and isoprenaline showed clearly stronger activity in glial cell cultures, yet their activity was much weaker than that of PACAP, whereas the effect of forskolin was only 2 times larger in glial cells than in neuronal cultures; histamine had no effect in any cell culture, while secretin produced a small but significant effect only in glial cells. The obtained results suggest that the astrocyte compartment of the rat brain may be the main target for such peptides as PACAP, VIP, or structurally related PHI/PHM or helodermin.