Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Its Receptors: Neuroendocrine and Endocrine Interaction

The recent progress of research on the functions of pituitary adenylate cyclase activating polypeptide (PACAP), especially endocrine and neuroendocrine interactions, is described. Studies of the genes encoding the PACAP precursor and the type I PACAP receptor provide information on the control of PACAP gene expression and on the relationship between the structure of the receptor subtypes and the activation of various signal transduction pathways. The availability of specific antisera against PACAP and the type I PACAP receptor made it possible to examine their distributions in the brain and other tissues. Immunohistochemical studies and physiological studies with synthetic PACAP indicate that PACAP is a new type of hypophysiotropic hormone and also functions as a neurotransmitter, neuromodulator, and neurotrophic factor in the central nervous system. The abundance of PACAP and its type I receptors in the adrenal medulla and the results of studies with synthetic PACAP suggest that PACAP is a potent noncholinergic secretogue for catecholamines. PACAP and its receptors are also present in the pancreas and appear to play a regulatory role in insulin secretion at extremely low concentrations in a glucose-dependent manner. Immunohistochemical demonstration of PACAP and its receptors in the testicular spermatids at early stages suggests an important role of testicular PACAP in spermiogenesis. Together with its actions on pituitary gonadotropes, this suggests that it plays a key role in reproduction.