Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis.
The involvement of the cholecystokinin (CCK)-A receptor in fever was studied. The polyphasic febrile responses to lipopolysaccharide (LPS; 10 microg kg-1, I.V.) were compared between wild-type Long-Evans (LE) rats and the CCK-A-receptor-deficient Otsuka LE Tokushima Fatty (OLETF) rats. The response of the wild-type rats was biphasic, which is typical for LE rats. Phases 1 and 2 of the response of the OLETF rats were similar to those of the LE rats, but the OLETF rats also developed a robust phase 3. This late enhancement of the febrile response could reflect either the absence of the A receptor per se or a secondary trait of the mutant strain. To distinguish between these possibilities, we conducted a pharmacological analysis. We studied whether the normally low phase 3 of LE rats can be enhanced by a CCK-A-receptor antagonist, sodium lorglumide (4.3 microg kg-1 min-1, 120 min, I.V.), and whether the normally high phase 3 of Wistar rats can be attenuated by a CCK-A receptor agonist, sulphated CCK-8 (up to 0.17 microg kg-1 min-1, 120 min, I.V.). The dose of sodium lorglumide used was sufficient to increase food intake (to block satiety), but it did not affect the fever response. In both febrile and afebrile rats, CCK-8 induced dose-dependent skin vasodilatation and decreased body temperature, but it failed to produce any effects specific for phase 3. We conclude that the exaggeration of phase 3 in OLETF rats reflects a secondary trait of this strain and not the lack of the CCK-A receptor per se. None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor.
Ivanov
Andrei I
AI
Trauma Research, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Kulchitsky
Vladimir A
VA
Romanovsky
Andrej A
AA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D017353:Gene Deletion; D006727:Hormone Antagonists / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016296:Mutagenesis; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000378:metabolism*; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology*
D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide