The Role of PACAP in the Regulation of Body Temperature

Abstract

Studies aiming at the investigation of the thermal effects of the pituitary adenylate cyclase-activating polypeptide (PACAP) revealed that PACAP plays an important role in the regulation of body temperature. We review literature data on the effects of pharmacological modulation of PACAP signaling on deep body temperature as well as on the influence of PACAP-signaling deficiency on thermoregulation in animals and humans. We describe the contribution of behavioral and autonomic thermoeffectors to the hyperthermic effect of PACAP and the thermoregulatory phenotype of mice genetically lacking the peptide. We propose that behavioral (hyperactivity, wet-dog shakes) and autonomic (non-shivering thermogenesis and cutaneous vasoconstriction) cold-defense responses are recruited in PACAP-induced hyperthermia. The absence of PACAP results in hypometabolism and as a compensatory mechanism in increased locomotor activity. We hypothesize that the thermal effects of PACAP are evoked through modulation of the cold-activated pathway in the preoptic area of the hypothalamus. Hyperthermia in response to exogenous PACAP administration develops through activation of γ-aminobutyric acid-ergic neurons located in the median preoptic nucleus, while the hypometabolism in PACAP deficiency is caused by the absent suppression of tonically activated γ-aminobutyric acid-ergic neurons in the medial preoptic area, which leads to enhanced inhibition of non-shivering thermogenesis. The contribution of other central nervous system regions to the thermoregulatory effects of PACAP is also discussed.