cholecystokinin and Hypothermia

Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with special emphasis on two types of responses, that is hyperthermia (fever) and hypothermia. Central microinjection of CCK in rats induces a thermogenic response that can be attenuated by CCK-B receptor antagonists, but some authors observed a hypothermia. By contrast to its central fever-inducing effect, in rodents exposed to cold CCK-8 elicits a dose-dependent hypothermia on peripheral injection probably acting on CCK-A receptors. 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. The possible role of CCK-ergic mediation in endotoxin (LPS) fever has revealed that while CCK-B receptors seem to be involved in the development of fever, the role of CCK-A receptors could be more complex. In particular, while rats lacking functional CCK-A receptors show an exaggerated fever response, this phenomenon 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 PGE mediation needs further study.

Topics: Animals; Central Nervous System; Cholecystokinin; Fever; Humans; Hypothermia; Rats

Prevailing changes in the feeding status or the nutritional status, in general, can modify the expression of many orexigenic and anorexigenic peptides, which influence hypothalamic functions. These peptides usually adjust body temperature according to anabolic (increased appetite with suppressed metabolic rate and body temperature) or catabolic (anorexia with enhanced metabolism and temperature) patterns. It was plausible to presume that such peptides contribute to regulated changes of body temperature (either fever or hypothermia) in systemic inflammation, particularly since anorexia is a common feature in inflammatory processes. No consistent, common, or uniform way of action was, however, demonstrated, which could have described the effects of various peptides. With the exception of cholecystokinin (CCK), all investigated peptides were devoid of real thermoregulatory actions: they influenced the metabolic rate (and consequently body temperature), but not the mechanisms of heat loss. Central CCK is indeed catabolic and may participate in febrigenesis. Leptin may activate various cytokines, catabolic peptides and may inhibit anabolic peptides, but it probably has no direct febrigenic effect and it is not indispensable in fever. Melanocortins and corticotropin-releasing factor provide catabolic adaptive mechanisms to food intake (diet induced thermogenesis) and environmental stress, respectively, but they act rather as endogenous antipyretic substances during systemic inflammation, possibly contributing to the mechanisms of limitation of fever. Bacterial lipopolysaccharides enhance the expression of most of these catabolic peptides. In contrast, neuropeptide Y (NPY) expression may not be changed, only its release is decreased at specific nuclei, a defective NPY effect may also contribute to the febrile rise in body temperature. The data provide no clear-cut explanation for the mechanism of hypothermia seen in systemic inflammation. According to speculations, a presumed, overflow,-type release of NPY from the hypothalamic nuclei, as well as a suppression of the activity of catabolic peptides, could possibly cause hypothermia. There are no cues, however, referring to the identity of factors that could trigger such changes during systemic inflammation in order to induce hypothermia.

Topics: alpha-MSH; Animals; Body Temperature; Cholecystokinin; Corticotropin-Releasing Hormone; Eating; Endotoxins; Fever; Humans; Hypothermia; Inflammation; Leptin; Mice; Neuropeptide Y; Peptides; Rats

Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with special emphasis on two types of responses, that is hypothermia or hyperthermia. In rodents exposed to cold a dose-dependent hypothermia has been observed on peripheral injection of CCK probably acting on CCKA receptors. Central microinjection of CCK in rats induced a thermogenic response that could be attenuated by CCKB receptor antagonists, but some authors observed a hypothermia. 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. Possible connections between thermoregulatory and other autonomic functional changes induced by CCK are discussed.

Topics: Animals; Cholecystokinin; Cold Temperature; Fever; Hypothermia; Peptides; Rats; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Temperature

The effects of cholecystokinin-8 sulfate (CCK-8), cholecystokinin-8 unsulfate (CCK-8U), cholecystokinin-4 (CCK-4), caerulein and morphine on mice core body temperature have been studied in the present work. Subcutaneous injection of different doses of caerulein (0.05, 0.1 and 0.5 mg/kg), CCK-8 (0.05, 0.1 and 0.25 mg/kg) and morphine (10, 20 and 30 mg/kg) induced hypothermia. CCK-8U and CCK-4 did not elicit any response. The hypothermic response induced by caerulein, a CCK-related decapeptide but not morphine was decreased by selective CCK(A) receptor antagonist MK-329. However, the hypothermia induced by morphine but not caerulein was reduced by opioid antagonist naloxone. When morphine plus caerulein was administered a higher hypothermia was induced. Pretreatment of animals with L-365 260, a selective CCK(B) receptor antagonist did not alter the hypothermia induced by the drugs. The response induced by combination of the both drugs was decreased by MK-329. Administration of CCK antagonists MK-329 and L-365 260 to mice did not exert any effect on temperature. It is concluded that the CCK(A) receptor mechanism may be involved in the hypothermic effect of CCK agonists or morphine, while opioid receptor mechanism is not involved in CCK receptor agonists' response.

Topics: Animals; Body Temperature; Ceruletide; Cholecystokinin; Hypothermia; Male; Mice; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Receptors, Cholecystokinin; Time Factors

Topics: Animals; Cholecystokinin; Hypothermia; Injections, Intraventricular; Male; Peptide Fragments; Rats; Rats, Inbred Strains; Sincalide

Topics: Animals; Cholecystokinin; Dogs; Gastrointestinal Hormones; Hypothermia; Hypothermia, Induced; Neurophysiology; Pancreas; Pancreatic Juice; Pharmacology; Physiology; Research; Secretin