VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic...

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as the three classes of G-protein-coupled receptors mediating their effects, are widely distributed in the central nervous system (CNS) and peripheral tissues. These peptides are reported to have many effects in different tissues, which are physiological or pharmacological, and which receptor mediates which effect, has been difficult to determine, primarily due to lack of potent, stable, selective agonists/antagonists. Recently the use of animals with targeted knockout of the peptide or a specific receptor has provided important insights into their role in normal physiology and disease states.

During the review period, considerable progress and insights has occurred in the understanding of the role of VIP/PACAP as well as their receptors in a number of different disorders/areas. Particularly, insights into their roles in energy metabolism, glucose regulation, various gastrointestinal processes including gastrointestinal inflammatory conditions and motility and their role in the CNS as well as CNS diseases has greatly expanded.

PACAP/VIP as well as their three classes of receptors are important in many physiological/pathophysiological processes, some of which are identified in these studies using knockout animals. These studies may lead to new novel treatment approaches. Particularly important are their roles in glucose metabolism and on islets leading to possible novel approaches in diabetes; their novel anti-inflammatory, cytoprotective effects, their CNS neuroprotective effects, and their possible roles in diseases such as schizophrenia and chronic depression.