This gene encodes adenylate cyclase-activating polypeptide 1. Mediated by adenylate cyclase-activating polypeptide 1 receptors, this polypeptide stimulates
adenylate cyclase and subsequently increases the
cAMP level in target cells. Adenylate cyclase-activating polypeptide 1 is not only a hypophysiotropic hormone (i.e. a substance that induces activity in the
hypophysis), but also functions as a
neurotransmitter and
neuromodulator. In addition, it plays a role in
paracrine and
autocrine regulation of certain types of cells. This gene has five
exons. Exons 1 and 2 encode the
5' UTR and
signal peptide, respectively; exon 4 encodes an adenylate cyclase-activating polypeptide 1-related peptide; and exon 5 encodes the mature peptide and
3' UTR. This gene encodes three different mature peptides, including two isotypes: a shorter form and a longer form. This disorder involves a maladaptive psychological response to traumatic, i.e. existence-threatening, events. Ressler et al. identified an association of a
SNP in the gene coding for pituitary adenylate cyclase-activating polypeptide (PACAP), implicating this peptide and its receptor (
PAC1) in PTSD. In mouse model of heavy alcohol drinking, PACAP seems to mediate alcohol effects on
bed nucleus of the stria terminalis.
Headache Disorders Both isoforms of PACAP (PACAP-38 and PACAP-27) have been implicated in
migraine pathogenesis. A Danish research group led by Dr.
Messoud Ashina found that intravenous infusion of PACAP-38 induced migraine attacks in 58% of people with migraine,
Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.
Neuroprotective PACAP has also been shown to be neuroprotective, though its tendency to induce migraines has limited clinical use of this property. == Interactions ==