Pituitary adenylate cyclase activating polypeptide (PACAP): An important neuropeptide in the peripheral nervous system

Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide (VIP)-family of regulatory peptides and is found in the sensory and autonomic subdivisions of the peripheral nervous system. PACAP and PACAP mRNA are present in small to medium-sized capsaicin-sensitive neurons of dorsal root ganglia (DRG) and in nerve fibers in the dorsal horn of the spinal cord. This indicates a role for PACAP as a sensory neuropeptide. In sympathetic ganglia, such as the superior cervical ganglion (SCG), PACAP-containing nerve fibers surround neurons expressing PACAP type 1 receptors suggesting that PACAP might be involved in the regulation of sympathetic activity. After axonal injury PACAP displays a considerable plasticity in expression. Thus in DRG, neuronal expression of PACAP and PACAP mRNA increases rapidly after sciatic nerve lesion mainly in. medium-sized to large neurons. Chemical sympathectomy using 6-hydroxydopamine (6-OHDA) leads to a massive upregulation of PACAP (but not PACAP type I receptor mRNA) in SCG, thus suggesting that PACAP and PACAP type I receptors are differentially regulated. PACAP appears to belong to a category of neuropeptides, including VIP and galanin, that are upregulated after axonal injury The functional significance of this upregulation is not known. Others have demonstrated that PACAP is a neurotrophic factor as well as a growth factor during development. The possibility that PACAP exerts such a role during regeneration must therefore be considered.