Pituitary adenylate-cyclase-activating polypeptide (acronym: PACAP) is a 27- or 38-amino acid neuropeptide that belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. PACAP has a particularly high homology (~ 68 %) to VIP. Due to the high homology of the amino acid sequences of PACAP and VIP, these peptides share three class B G-protein-coupled receptors:
These receptors have a high homology to each other and their high homology is exploited for these discoveries. This review mainly gives an overview of the history of the discovery of PACAP and its three receptors.
PACAP is mainly expressed in nervous tissues, where its receptors are also widely distributed. PACAP and its receptors are involved in various biological functions. Peripherally, they are involved in the control of anterior pituitary hormone secretion, vasodilation, adrenaline release, insulin secretion and immunosuppression. In the central nervous system, PACAP not only acts as a neurotransmitter, but also exerts a neuroprotective effect in brain ischemia, Parkinson's disease, traumatic brain injury and spinal cord injury.
It has been reported that mice with a PACAP gene deficiency develop symptoms similar to dry eye, such as corneal keratinization and tear reduction. It has also been demonstrated that injection of PACAP into the soles of the feet of mice significantly promotes sweat secretion at the injection site. These reports suggest that PACAP may also prove clinically useful for the treatment of dry eyes and sweating problems.