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PubMed1997

Effect of a cholecystokinin-A receptor blocker on protein-induced food intake suppression in rats.

To test the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via cholecystokinin (CCK) receptors, devazepide was coadministered with each macronutrient. Given alone (in 4 ml ig), Pro (0.75, 1.0, and 1.5 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed (P < 0.05) food intake in the first hour by 0.5, 0.8, and 1.1 g; 1.9 g; and 1.0 g, respectively, and in the first 2 h of feeding by 0.8, 1.2, and 1.3 g; 1.7 g; 0.7 g; and 1.5 g, respectively. When coadministered with devazepide (0.5 mg/kg body wt ig), the suppression of food intake caused by Pro, AA, CHO, and Fat treatments was modulated in the first hour by 60, 50, and 55%; 16%, 11%; and 10%, respectively, and during 0-2 h by 63, 92, and 54%; 29%; 0%; and -20%, respectively. Devazepide (0.5 mg/kg) given intraperitoneally also modulated Pro intake suppression during the first hour by 33% and during 0-2 h by 79%. Devazepide appears to interact with mechanisms of Pro-induced food intake suppression, but not AA-, Fat-, or CHO-induced food intake suppression. These studies provide evidence that CCK receptors play a role in Pro (albumin)- but not AA-, CHO (corn starch)-, or Fat (corn oil)-induced food intake suppression in rats.

Amino Acids↗
PubMedDate not supplied

Peripheral cholecystokinin A and cholecystokinin B receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate.

BACKGROUND: Peptides of cholecystokinin family regulate various physiological actions by acting at level of central nervous system. AIMS: To: 1) investigate possible influence of central cholecystokinin pathways on gastric pepsinogen and acid secretions; 2) characterize pharmacological profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecystokinin-8S). METHODS: Urethane-anaesthetized rats were subjected to continuous perfusion of gastric lumen. Pepsin levels in perfusate were determined by enzymatic assay based on spectrophotometric measurement of products generated by peptic digestion of bovine haemoglobin. Acidity was measured by automatic potentiometric titration of hydrogen ions. RESULTS: Following intracerebroventricular injection, cholecystokinin-8S increased both pepsinogen and acid output. In addition, intravenous cholecystokinin-8S stimulated peptic and acid secretions more promptly and at lower doses than after central injection. Stimulant effects of centrally applied cholecystokinin-8S were not affected by intracerebroventricular injection of devazepide (cholecystokinin A receptor antagonist) or L-365,260 (cholecystokinin B receptor antagonist) or by bilateral vagotomy. However, intravenous devazepide partly antagonized pepsigogue action of intracerebroventricular cholecystokinin-8S without affecting its acid hypersecretory effect, whereas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and acid response was completely blocked. Similar effects were exerted by intravenous devazepide and L-365,260 against intravenous cholecystokinin-8S. A complete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous treatment with devazepide plus L-365,260. Gastric hypersecretory effects of intravenous cholecystokinin-8S were not modified by bilateral vagotomy. CONCLUSIONS: Increase in pepsinogen output evoked by centrally applied cholecystokinin-8S does not depend on interaction with central nervous sites. Following central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecystokinin A and B receptors presumably located at the level of gastric mucosa.

Analysis of Variance↗
PubMed1999

CCK stimulates growth of both the pancreas and the liver.

BACKGROUND: The pancreas is the main target of the trophic effect of cholecystokinin (CCK), with a transient increase in cell proliferation and persistent effect on DNA content and weight gain when given continuously. Whether CCK exerts similar effects on the liver and biliary tract is not known. Most studies on this subject have hitherto been done in the rat. The aim of the present experiments was therefore to study the possible concomitant trophic effects of CCK on these three organs in a gallbladder-bearing animal, the hamster. METHODS: CCK-8S or the CCK-A receptor antagonist devazepide were infused subcutaneously by osmotic minipumps for 4 weeks in 11 and 7 hamsters, respectively. Fifteen animals served as untreated controls. One hour before sacrifice tritiated thymidine was injected intraperitoneally. Plasma was collected for determination of CCK and the pancreas, liver, common bile duct and gallbladder were excised. The pancreas and liver were weighed and processed for the contents of protein, DNA and water. Tissue specimens were taken for autoradiography. RESULTS: The concentration of CCK in plasma increased fourfold during the infusion of CCK-8S. The pancreas and, to a lesser extent, the liver increased in weight, DNA and protein contents after infusion of CCK-8S, whereas the pancreas, but not the liver, decreased in weight and protein content after infusion of devazepide. Pancreatic amylase content was increased after CCK-8S treatment, but unaffected by devazepide. Labelling index of pancreatic acinar cells, hepatocytes and gallbladder epithelium was no different from that of controls after four weeks of infusion of CCK-8S or devazepide. A correlation was found between the concentration of plasma CCK on one hand and the weights and DNA contents in pancreas and liver on the other. CONCLUSION: The results suggest that CCK stimulates growth of both the pancreas and the liver in the hamster.

Animals↗
PubMed1993

[Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in amygdala of the rat].

CCK-8 administered bilaterally to the amygdala at 0.1-1.0 ng dose-dependently antagonized the analgesia induced by morphine (4 mg/kg, s. c.) as measured by the changes in tail flick latency (TFL). This effect of CCK-8 could be reversed by Devazepide, a CCK-A receptor antagonist dose-dependently at 50 ng and 200 ng, and by L-365, 260, a CCK-B receptor antagonist at 5 ng and 8 ng administered to the same site. The effect of morphine analgesia was potentiated by 200 ng Devazepide or 8 ng L-365, 260 administered bilaterally to amygdala. Devazepide and L-365, 260 per second showed no significant influence on basal TFL. The results indicate that amygdala is a strategic site where CCK-8 exerts an antiopioid activity. Since the effect of L-365, 260 was 25 times more potent than Devazepide, it suggests that the anti-opiod effect of CCK in amygdala is mediated by CCK-B receptors.

Amygdala↗
PubMed1997

The effect of drugs acting on CCK receptors and rat free exploration in the exploration box.

The effects of cholecystokinin (CCK) CCKA receptor antagonist devazepide (10 micrograms/kg and 1.0 mg/kg), CCKB receptor antagonist L 365260 (1.0 mg/kg), and CCKB receptor agonist CCK tetrapeptide (CCK-4, 75 micrograms/kg), and their concomitant administration with antidepressants desipramine (10 mg/kg) and citalopram (10 mg/kg) on rat exploratory behaviour were studied in the recently developed exploration box test. In addition, the effects of repeated administration of despiramine (10 mg/kg) and citalopram (10 mg/kg) were studied. After acute administration, CCK-4 decreased significantly the number of line crossings, rears, investigative approaches, and the time spent exploring. The time of latency and the number of entries into large arena were unchanged. Desipramine reduced all observed criterions of rat behaviour, but citalopram was ineffective. Devazepide (1.0 mg/kg) and L 365260 (1.0 mg/kg) had no effect on rat behaviour after acute or repeated administration. L 365260 (1.0 mg/kg) blocked the antiexploratory effect of CCK-4, whereas devazepide (10 micrograms/kg) did not. No interaction of CCK-4, devazepide, or L 365260 treatment with antidepressant treatment was found. Our results suggest that the administration of a CCKB agonist diminishes rat exploratory behaviour, but neither CCKA nor CCKB receptor blockade induces changes on rat exploratory behaviour in the free exploration paradigm.

Adrenergic Uptake Inhibitors↗
PubMed1999

The expression of behavioral sensitization to amphetamine: role of CCK(A) receptors.

These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment.

Amphetamine↗
PubMed2000

Cholecystokinin modulates both the development and the expression of behavioral sensitization to amphetamine in the rat.

RATIONALE: Repeated administration of psychostimulants such as amphetamine (AMPH) produces an enduring augmentation of their locomotor effects. Previous research suggests that this phenomenon, termed sensitization, is related to changes within the mesolimbic dopamine (DA) system. OBJECTIVES: The present experiments were designed to investigate the contribution of endogenous cholecystokinin (CCK), a neuropeptide co-localized with DA in the mesolimbic system, to the development (experiment 1) and the expression (experiment 2) of locomotor sensitization to AMPH. METHODS: In experiment 1, rats were injected (IP) with the CCK(A) antagonist devazepide (0, 0.001, 0.01, or 0.1 mg/kg) or the CCK(B) antagonist L-365,260 (0, 0.001, 0.01, 0.1, or 1.0 mg/kg) followed by AMPH (1.5 mg/kg) once daily for seven days. Following 10 days withdrawal, rats were administered AMPH (0.75 mg/kg) and their locomotor activity recorded. In experiment 2, rats were administered AMPH (1.5 mg/kg) once daily for 7 days. Following 10 days withdrawal, rats were injected with devazepide (0, 0.0001, 0.001, 0.01, 0.1, or 1.0 mg/kg) or L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg) followed 30 min later by AMPH (0.75 mg/kg) and their locomotor activity recorded. RESULTS: When administered during the AMPH pretreatment phase of experiment 1, the two highest doses of L-365,260 attenuated, and the lowest dose of L-365,260 potentiated, the sensitized locomotor response to AMPH challenge. When administered prior to the AMPH challenge phase of experiment 2, devazepide attenuated the sensitized locomotor response to AMPH. CONCLUSIONS: These results suggest that CCK(B) and CCK(A) receptors modulate the development and the expression of behavioral sensitization to AMPH, respectively.

Amphetamine↗
PubMed1994

Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor.

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng) administered bilaterally to the nucleus accumbens of the rat. This effect of CCK-8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti-opioid activity, most probably via the CCK-B receptors.

Animals↗
PubMed1994

The influence of 5-hydroxytryptamine re-uptake blockade on CCK receptor antagonist effects in the rat elevated zero-maze.

In this study, the elevated zero-maze model of anxiety was used to investigate CCK receptor antagonist effects on the behaviour of male Lister-hooded rats and to demonstrate, by administering antagonists in the presence or absence of selective 5-hydroxytryptamine (5-HT) re-uptake inhibitors, the involvement of 5-HT in the mediation of these effects. Devazepide, a selective CCKA receptor antagonist, L-365,260 (3R(+)-N-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin- 3-yl-N1- (3-methyl-phenyl)urea) or CI-988 (4-([2-[[3-(1H-indol-3-yl)-2-methyl-1- oxo-2-[[(tricyclo[3.3.1.1.(3.7)]-dec-2-yloxy)-carbonyl]-amin o]- propyl]-amino]-1-phenylethyl]-amino)-4-oxo-[R-(R*,R*)]-butanoate- N-methyl-D-glucamine), both selective CCKB receptor antagonists, were administered 30 min prior to testing. Behavioural analysis during testing included measures of risk-assessment behaviours (e.g. stretched-attend posture) in addition to time spent on the open quadrants. Devazepide induced significant anxiolytic effects, whereas CI-988 produced inconsistent results and L-365,260 was ineffective. When administered simultaneously with the 5-HT re-uptake inhibitors zimelidine or Wy 27587 (N-[[[1-[(6- fluoro-2-naphthalenyl)methyl]-4-piperidinyl]amino] carbonyl]-3-pyridine carboxamide methyl sulphonate salt), the significant anxiolytic effect induced by devazepide was dose-dependently and significantly attenuated. Zimelidine and Wy27587 had little effect alone on zero-maze behaviour at the lower of two doses given. These data show that the elevated zero-maze, in conjunction with the analysis of 'risk-assessment' behaviours, is an anxiety model which is sensitive to the anxiolytic effects of CCK receptor antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Possible role of cholecystokinin-A receptors in regulation of thyrotropin (TSH) secretion in male rats.

We studied the importance of cholecystokinin (CCK) system in the regulation of thyrotropin (TSH) and prolactin (PRL) secretion in male rats. To this end, we tested the effects of both unselective CCK agonists CCK-8 and caerulein, and CCK-B selective agonists CCK-4 and pentagastrin as well as the selective CCK antagonists (devazepide and L-365,260) at wide dose-ranges on the cold-stimulated and TRH-induced TSH and PRL secretion. Caerulein, given s.c. 15 min before sacrifice, decreased TSH levels at 5 micrograms/kg. In time course-studies, the maximum inhibition was seen at 15 min but the effect lasted at least 30, but less than 60 min. Also CCK-8 decreased TSH levels at the doses of 20 and 50 micrograms/kg at 15 min. Devazepide and L-365,260 did not affect TSH or PRL levels at any dose. The effect of caerulein (5 micrograms/kg) was antagonized by devazepide, a CCK-A antagonist, at 100 micrograms/kg, but not by a CCK-B antagonist L-365,260 tested at a wide dose range. PRL levels were not affected by any treatment. Caerulein (5 micrograms/kg), given at the same time as TRH (500 ng/kg), inhibited the TRH-induced TSH levels at 15 min, but not at 30 or 60 min. CCK-8 (50 micrograms/kg), CCK-4 (100 micrograms/kg) and pentagastrin (500 micrograms/kg) did not affect the TRH-induced TSH secretion. The results probably indicate that CCK-A receptor stimulation inhibits TSH secretion at the level of the anterior pituitary gland. PRL levels in male rats are not affected by CCK system.

Animals↗
PubMed1995

Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors in the vagal pathway and gallbladder in the dog.

The mechanism of CCK action on gallbladder contractions in the physiological condition is unclear. Gallbladder contractions were monitored by means of chronically implanted force transducers in conscious dogs. Postprandial gallbladder contractions were partially inhibited by atropine and hexamethonium, and completely inhibited by devazepide. In vitro contractile response of canine gallbladder muscle strips to CCK-8 was also studied. CCK-8-induced muscle strip contraction was atropine and tetrodotoxin resistant, but was completely eliminated by devazepide. The existence of CCK receptors in the vagal nerve and gallbladder was examined by means of autoradiography. Forty-eight hours after ligation of the abdominal vagus, CCK-8 binding sites were found to accumulate in the subdiaphragmatic vagal nerve immediately proximal to the ligature, and similar binding sites were also found in the gallbladder smooth muscle layer. These binding sites were displaced by the addition of 10(-7) mol/1 unlabeled CCK-8 and devazepide, but L-365,260 had no effect. In conclusion, it is considerable that postprandial CCK-induced gallbladder contractions are controlled through CCK-A receptors both on the vagal nerve in stimulating endogenous release of acetylcholine and on the gallbladder directly to stimulate muscle contraction in the dog.

Animals↗
PubMedDate not supplied

Different effects of CCK antagonists on gastric-acid response to CCK and pentagastrin.

The role of CCK receptor subtypes in peptide-stimulated acid secretion was assessed in six unanesthetized rats. The CCK-stimulated acid secretion was not blocked by L-365,260, a CCKB/gastrin receptor antagonist, and was significantly increased by devazepide, a CCKA receptor antagonist, given alone or together with L-365,260. L-365,260, but not devazepide, blocked pentagastrin-stimulated acid secretion, and, when given together, devazepide abolished the effect of L-365,260. We conclude: 1) pentagastrin stimulates acid secretion through a gastrin-type receptor, but CCK may not, and 2) pentagastrin and CCK can stimulate acid secretion despite simultaneous blockade of CCKB/gastrin and CCKA receptors.

Animals↗
PubMed2004

Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine.

Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in the CNS may be important in the pathogenesis of psychotic disorders and substance abuse. In this study, the effect of coadministration of the selective CCK receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and CCK2 receptors, respectively), on the effect of amphetamine on the rat exploratory behavior, and on sensitization of locomotor response to amphetamine, were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the exploration box for 5 consecutive testing days, while devazepide (10 microg/kg) blocked and L-365,260 (10 microg/kg) enhanced amphetamine-induced stimulation of activity. Devazepide coadministration prevented the development of sensitization to amphetamine, while coadministration of L-365,260 with amphetamine potentiated the locomotor effect of a challenge dose of amphetamine. These results suggest that endogenous CCK, released during exploratory activity, shapes behavioral responses to amphetamine by acting on both receptor subtypes, and modulates the development of sensitization to amphetamine.

Amphetamine↗
PubMed2001

Endogenous cholecystokinin plays a role in down-regulation of pancreatic amylase independent of dietary carbohydrate in rats.

The role of cholecystokinin (CCK) in the regulation of pancreatic amylase has not been fully clarified. We examined the effects of hyperCCKemia with chronic pancreatico-biliary diversion (PBD) and blockade of CCK(A)-receptor on rat pancreatic amylase activity and mRNA abundance. Also, we examined the relationship between diet and CCK in terms of regulation of pancreatic amylase. PBD was produced by transposition of the duodenal segment containing the ampulla of Vater to the upper ileum. A potent CCK(A)-receptor antagonist, devazepide, was injected (6 mg/kg body weight per day for 5 days) in the PBD rats fed with diets containing normal or low level of carbohydrate (695 or 345 g sucrose/kg diet). The specific activity and mRNA abundance of the pancreatic amylase were constantly lower 4, 10 and 28 days after PBD than those after the sham operation. Devazepide treatment completely restored the amylase activity lowered by PBD without any increases in amylase mRNA. Feeding a high-protein low-carbohydrate diet suppressed the pancreatic amylase activity and mRNA abundance in PBD rats to a similar degree in those treated, and those untreated, with devazepide. We conclude that endogenous CCK suppresses pancreatic amylase production, and we speculate that CCK reduced translational efficiency of amylase mRNA. The effect of CCK on amylase production is independent of regulation by dietary carbohydrate.

Amylases↗
PubMed1999

Cyclic estradiol treatment phasically potentiates endogenous cholecystokinin's satiating action in ovariectomized rats.

The influence of ovarian cycling and of exogenous estradiol on the cholecystokinin (CCK) satiety-signalling system was investigated in intact and ovariectomized Long-Evans rats, respectively. Intraperitoneal injection of 1 mg/kg devazepide, the most potent and selective CCK(A) receptor antagonist, increased test meal size during estrus, but not during diestrus, confirming the influence of hypothalamic-pituitary-gonadal function on CCK satiety in intact rats. Devazepide was then tested in ovariectomized rats that received chronic cyclic estradiol (2 microg estradiol benzoate on Tuesday and Wednesday each week) or oil treatment. Devazepide did not increase meal size in estradiol-treated rats on Tuesday, prior to estradiol treatment, compared to oil-treated rats, but did selectively increase meal size on Friday, late in the estradiol replacement cycle, compared to Tuesday, early in the cycle. These results suggest that a phasic potentiation of the endogenous CCK satiety-signalling system is part of the mechanism for the decrease in meal size in female rats during estrus.

Animals↗
PubMed1999

Endogenous cholecystokinin's satiating action increases during estrus in female rats.

Food intake and meal size are reduced in female Long-Evans rats during estrus. To investigate the contribution of the satiating action of endogenous cholecystokinin (CCK) to this, rats were injected with 1 mg/kg of the potent, selective CCK(A) receptor antagonist, devazepide, during diestrus, when meal size is maximal, and during estrus, when it is minimal. Devazepide increased spontaneous food intake and meal size during estrus, but not during diestrus. Meal frequency was not affected by devazepide treatment. These results indicate that the potency of the CCK satiety-signaling system increases during estrus.

Animals↗
PubMed1997

Cholecystokinin receptors mediate the development of a preference for the mother by newly born lambs.

The aim of this study was to investigate the effect of selective cholecystokinin (CCK) antagonists on the development of a preference for the mother by newly born lambs. At birth lambs received an injection of the CCK-A antagonist devazepide (0.01 or 0.1 mg/kg), the CCK-B antagonist PD135158 (0.01 or 0.1 mg/kg), or saline for the controls (1 ml/kg). No major side effects were observed in the first 4 postnatal hours except that lambs receiving PD135158 displayed more exploratory behavior towards the maternal body than lambs from the other groups. When tested in a 2-choice test situation at 24 hr of age, lambs treated with PD135158 or saline spent significantly more time near their dams than near the alien ewes, whereas lambs treated with devazepide did not show any discrimination. The effect of devazepide persisted at 48 hr of age. The use of a CCK-A antagonist, but not a CCK-B antagonist, was concluded to prevent the formation of a preferential relationship between the lamb and its mother, most probably by impairing neonatal learning.

Animals↗
PubMed1999

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.

Adrenal Glands↗