PACAP--a multifacetted neuropeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) was originally isolated from ovine hypothalamus based on its ability to stimulate cAMP production in pituitary cell cultures. The peptide exists in two forms, both of which are derived from the same precursor. PACAP38 and the C-terminal truncated PACAP27 can interact with three subtypes of receptors activating adenylate cyclase and/or phospholipase C. Since its discovery, numerous studies have provided evidence that PACAP is a pleiotropic substance having a broad spectrum of biological functions; the peptide can act as a hormone, neurohormone, autocrine/paracrine substance, neurotransmitter, neuromodulator, neurotrophic factor, and immunomodulator. Two examples of the functional role of PACAP on the biological timing system are presented: 1) the transient expression of PACAP during the periovulatory period in ovarian cells, in which PACAP functions as an autocrine/paracrine inducer of progesterone secretion and subsequent luteinization; and 2) the role of PACAP as a neurotransmitter in the retinohypothalamic tract mediating photic regulation of the brain's biological clock.