Pituitary adenylyl cyclase activating peptide; a neuropeptide expressed in nervous system where it functions to regulate cellular communication. PACAP has emerged as a likely retinal messenger to the suprachiasmatic nucleus (SCN), acting in concert with glutamate to communicate photic information to the circadian system. PACAP-like immunoreactivity is found in terminals of retinal ganglion cells (RGCs) innervating the SCN and two of the receptors sensitive to PACAP (PAC1 and VPAC2) are expressed in the SCN. To date, all of the available evidence indicates that the PAC1 receptor is responsible for mediating the effects of PACAP on SCN neurons.

Mechanistically, PACAP pre-synaptically enhances the release of glutamate onto SCN neurons and postsynaptically enhances the magnitude of the response to glutamate within the SCN. PACAP can also increase calcium in SCN neurons by causing a release from intracellular stores as well as an enhancement of voltage-dependent calcium currents....