Evidence that cholecystokinin receptors are not involved in the hypothalamic-pituitary-adrenal response to intraperitoneal administration of interleukin-1beta.
The purpose of this study was to investigate a putative role for cholecystokinin (CCK) in the activation of the hypothalamic-pituitary-adrenal (HPA) axis following intraperitoneal (i.p.) administration of interleukin-1-beta (IL-1beta). Previous studies predict that CCKA receptors on vagal sensory afferents may be involved in the initiation of the stress response following an acute i.p. injection of IL-1beta. Adult male rats were given an i.p. injection of a specific CCKA (devazepide, 1 mg/kg) or CCKB (CI-988, 1 mg/kg) receptor antagonist, 30 min prior to an i.p. injection of rat recombinant IL-1beta (rrIL-1beta), 0.5 microg/kg in 0.9% sterile saline/0.01% rat serum albumin. Blood samples were obtained via an indwelling jugular vein catheter, and the plasma levels of the stress hormones ACTH (adrenocorticotropin hormone) and corticosterone analysed over time as an indicator of HPA axis activation. This dose of rrIL-1beta resulted in a significant release of ACTH and corticosterone, peaking at 30-60 min, and returning to basal levels by 2 h. Pretreatment with either devazepide or CI-988 had no effect on the rrIL-1beta induced ACTH or corticosterone release. In contrast, the same dose of devazepide completely inhibited the ACTH and corticosterone response to i.p. CCK (octapeptide, sulphated form, CCK-8S), 5 microg/kg. It is concluded that CCK receptors are not involved in the hormonal stress response to a submaximal i.p. dose of rrIL-1beta.
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Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109-0720, USA. heididay@umich.edu
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D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D003345:Corticosterone / Q000097:blood; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007211:Indoles; D007375:Interleukin-1; D011949:Receptors, Cholecystokinin; D011994:Recombinant Proteins; C065599:PD 134308; D008536:Meglumine; D000324:Adrenocorticotropic Hormone; D020109:Devazepide; D003345:Corticosterone