Cholecystokinin: role in thermoregulation and other aspects of energetics

Abstract

Cholecystokinin (CCK) has long been implicated in body energetics, first as a gastrointestinal hormone assisting fat utilization and later as a neuropeptide acting either peripherally or centrally in the regulation of body mass. In the present review the thermoregulatory role of CCK peptides is reviewed with special emphasis on two types of responses, that is hyperthermia (fever) or hypothermia. Central microinjection of CCK in rats induces a thermogenic response that can be attenuated by CCK2 receptor antagonists, but some authors observed a mild hypothermia. By contrast to its central fever-inducing effect, CCK-8 elicits a dose-dependent hypothermia on peripheral injection probably acting on CCK1 receptors in rodents exposed to cold. It is suggested that neuronal CCK may have a specific role in the development of hyperthermia and endogenous CCK-ergic mechanisms could contribute to the mediation of fever. Recent evidence in rodents lacking either of the CCK receptors appears to support the fever-mediating role of the peptide. In particular, CCK2 receptors seem to be involved in the development of endotoxin fever, while the role of CCK1 receptors could be more complex. In line with that idea, rats lacking functional CCK1 receptors show an exaggerated fever response, a phenomenon that may be associated with a trait different from the absence of this receptor set. The relationship between the putative CCK-ergic febrile mechanism and the established central prostaglandin mediation is also discussed.