PACAP-38 is identical in mammals, from mice and rats to pigs, sheep and humans. PACAP has been shown to regulate gastric acid secretion and may be involved in the control of food and water intake. PACAP regulates the neuroimmune network by modulating the secretions of the pituitary and adrenal glands. In the nervous system, PACAP acts as a neurotransmitter and neuromodulator and can prevent neuron cell death in inflammatory disorders of the central nervous system. Studies indicate that PACAP may have a role in the development of cerebellum and cerebral cortex. In addition, higher brain functions are affected by PACAP. PACAP-38 is a potent pharmacological “trigger” of migrain-like attacks. Deficiency of PACAP and PACAP-specific receptor PAC1 in mice causes schizophrenia-like symptoms. Further, single-nucleotide polymorphism association studies have shown a relation of PACAP and PAC1 genes to schizophrenia. Matsuzaki, S and Tohyama, M., Expert Opin. Ther. Targets., 12, 1097 (2008); Fahrenkrug, J., Chronobiol. Int., 23, 53 (2006); Tan Y.V. et al., Proc. Natl. Acad. Sci. USA, 106, 2012 (2009), Ashina H, et al., J. Headach Pain, 16, 110 (2017).
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