Neurotransmitter and Immunomodulatory Actions of VIP and PACAP: Lessons from Knockout Mice

Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylyl Cyclase Activating Peptide (PACAP) are two closely related neuropeptides in the secretin family. They are widely expressed in the central and peripheral nervous systems, where they are classically thought to act as neurotransmitters or neuromodulators. They interact with high affinity receptors to regulate numerous behaviors as well as gastrointestinal, endocrine, cardiopulmonary, reproductive and immune functions. The recent generation of mice that specifically lack or overexpress VIP, PACAP or their receptors has yielded much new knowledge and enabled investigators to better understand the biological roles of these peptides and their impact on health. In this review, we attempt to summarize the major findings, but focus in greatest detail on the circadian and immune functions.