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PubMed1994

Neuroprotective effect of cholecystokininB receptor antagonist on ischemia-induced decrease in CA1 presynaptic fiber spikes in rat hippocampal slices.

The effects of cholecystokinin (CCK) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collaterals were investigated using rat hippocampal slices. Treatment with the CCKB receptor agonist CCK tetrapeptide (CCK4, 0.01-10 microM) exacerbated the ischemia-induced decrease in the CA1 presynaptic potential in a concentration-dependent manner. Whereas, treatment with the CCKB receptor antagonist [(3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-N1-(3-methylphenyl)-urea] (L365260), and not with CCKA receptor antagonist [(3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-1H-indole-2-carboxamide] (L364718), produced a concentration-dependent attenuation of the ischemia-induced decrease. The magnitude of recovery of the CA1 field potentials in L365260-treated groups at 10 and 100 nM was 34% and 45%, respectively. The neuroprotective effect of L365260 (0.01 and 0.1 microM) was completely blocked by co-treatment with CCK4 (0.1 microM), a concentration that did not affect the decreased presynaptic potential induced by ischemia. These results demonstrated that the stimulation of the CCKB receptor played a detrimental role in the development of ischemic damage, whereas the blockade of CCKB receptors played a neuroprotective role in ischemic damage, suggesting a facilitatory role of CCK receptor-operated function in ischemia-induced neuronal deficits.

Animals↗
PubMed1995

CCKB receptor activation protects CA1 neurons from ischemia-induced dysfunction in stroke-prone spontaneously hypertensive rats hippocampal slices.

We examined the effect of cholecystokinin octapeptide sulfated type (CCK-8S) on dysfunction of CA1 pyramidal neurons induced by in vitro ischemic insult in hippocampal slices of stroke-prone spontaneously hypertensive rats (SHRSP). CCK-8S shortened the time required for partial recovery from block of a population spike produced by ischemia. Furthermore, CCK-8S reduced ischemic insult-induced accumulation of K+ in extracellular space. Suppression of the K+ conductance by the CCKB receptor activation is suggested to contribute to neuroprotection by CCK-8S.

Animals↗
PubMed1995

Central administration of cholecystokinin stimulates gastric pepsinogen secretion from anaesthetized rats.

Intracerebroventricular administration of CCK-8S was associated with a stimulation of gastric pepsinogen secretion from anaesthetized rats; similar effects were induced by CCK-8S given intravenously. The excitatory effect of intracerebroventricular CCK-8S was not modified by central injection of L-364,718 or L-365,260, whereas both these antagonists, given by intravenous route, prevented the pepsigogue action of parenteral CCK-8S. Intracerebroventricular or intravenous CCK-8S also increased basal acid secretion, this latter effect being prevented by parenteral L-365,260 but not L-364,718. It is suggested that centrally applied CCK-8S evokes pepsinogen secretion through the activation of peripheral CCK-A and CCK-B receptors.

Anesthesia↗
PubMed1993

Cholecystokinin-induced ventral root depolarization of neonate rat hemicord in vitro.

1. Sulphated cholecystokinin octapeptide (CCK8S, 0.03-1.00 microM), pentapeptide (CCK5) and tetrapeptide (CCK4) elicited concentration dependent depolarizations of neonate rat ventral roots in vitro. 2. CCK5 was equipotent with CCK8S although CCK4 was weaker (equipotent molar ratio 17.5). 3. CCK8S-induced depolarizations were depressed by tetrodotoxin (0.1 microM), Mg2+ ions (0.75 mM) and the NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5, 10 microM). These results suggest that CCK8S-induced depolarizations were predominantly mediated through the release of an excitatory amino acid from interneuronal sites. 4. The selective CCKA and CCKB receptor antagonists, L-364,718 and L-365,260 both depressed CCK8S-induced depolarizations. CCK8S dose ratios in the presence of 1 microM L-364,718 or L-365,260 were 4.5 and 11.2 respectively, suggesting the response was mediated predominantly through stimulation of CCKB receptors. 5. These results suggest that the neonate rat hemicord preparation is a suitable tissue for functional CCK receptor assays.

2-Amino-5-phosphonovalerate↗
PubMed1992

Cholecystokinin: critical role in mediating olfactory influences on reproduction.

Our electrophysiological studies in female mice have demonstrated that electrical stimulation of the accessory olfactory bulb excites tuberoinfundibular dopaminergic arcuate neurons via the amygdala-stria terminalis route. This study shows that the medial preoptic area is identified as an additional relay for the excitatory transmission by examining the effectiveness of locally infused lignocaine anaesthetic in blocking the transmission and that of electrical stimulation in evoking a shorter latency response. Based on the known immunohistochemical findings, further attention is focused on a transmitter mediating synaptic transmission in the medial preoptic area. The cholecystokinin-B type receptor antagonist L-365,260 (0.3, 0.6, 0.9 pmol), but not the A type receptor antagonist L-364,718 (0.9 pmol), infused into the medial preoptic area, blocked the excitation of tuberoinfundibular arcuate neurons in a dose-dependent manner. Conversely, cholecystokinin octapeptide (0.6 pmol) increased firing activity in such neurons. The antagonizing effect of L-365,260 was reproduced in the context of the olfactory block to pregnancy: bilateral infusions of this drug into the medical preoptic area of recently mated females immediately before exposures to strange males' pheromones prevented them from inducing pregnancy block. These findings implicate cholecystokinin acting on cholecystokinin-B receptors in the medial preoptic area as a mediator of olfactory influences on reproductive physiology.

Animals↗
PubMed1991

CCK-8 modulates D2 receptor agonist-induced hypermotility in the nucleus accumbens.

The influence of CCK-8 on locomotor effects associated with independent D2 receptor stimulation was studied. To selectively stimulate mesolimbic D2 receptors LY 171555 was injected into the nucleus accumbens of awake rats. Locomotor activity was measured in the open-field test. LY 171555 induced a biphasic effect: low doses stimulated, whereas higher doses inhibited locomotor activity. CCK-8 injected into the posteromedial part of the nucleus accumbens suppressed hyperlocomotion induced by LY 171555. The CCK-8 effect was prevented by the CCK-antagonist L 364,718. Our results indicate that CCK-8 modulates D2 receptor-mediated effects in the mesolimbic system.

Animals↗
PubMed1994

Effects of cholecystokinin antagonists on the discriminative stimulus effects of cocaine in rats and monkeys.

Cholecystokinin (CCK) has been implicated as a modulator of dopamine (DA) neurotransmission in the mesolimbic DA pathway, a primary pathway implicated in the effects of cocaine related to its abuse. The present experiment was designed to examine whether an antagonist that acts at either CCKA or CCKB receptors can modify the discriminative stimulus effects of cocaine in animals. Rats (N = 9) and rhesus monkeys (N = 3) were trained in two-lever drug discrimination paradigms to discriminate cocaine from saline. Lever pressing was maintained by food (all rats, two monkeys) or shock avoidance (one monkey). In rats, the CCKA antagonist MK-329 (1.0-32 mg/kg, i.p.) or the CCKB antagonist CI-988 (1.0-32 mg/kg, i.p.) were administered 30 min before determination of cocaine dose-response functions using a cumulative dosing method. In monkeys, CI-988 (8.0-32 mg/kg, i.m.) was administered 30, 60 or 120 min before the training dose of cocaine. In both species, cocaine produced dose-related increases in the percentage of responses emitted on the cocaine-appropriate lever. In rats, MK-329 shifted the cocaine dose-response function to the right in a dose-related manner. In contrast, CI-988 did not systematically alter the effects of cocaine in either rats or monkeys. Since drug discrimination serves as an animal model of the subjective effects of drugs in humans, these results suggest that CCKA antagonists may decrease the subjective effects of cocaine. It seems unlikely that CCKB antagonists will alter the subjective effects of cocaine.

Animals↗
PubMed1995

Action of CCK on CDE diet-induced acute pancreatitis in rats treated with hydrocortisone.

The present work studies the effect of previous hydrocortisone administration (10 mg/kg/day) over 7 days on the later development of diet-induced acute pancreatitis in the rat. Acute pancreatitis was induced by feeding a diet deficient in choline and supplemented with 0.5% ethionine (CDE diet) over 10 days. Hydrocortisone pretreatment exacerbated CDE-induced acute pancreatitis. There was a significant increase in serum amylase, pancreatic edema, and haematocrit levels and an insignificant decrease in pancreatic mass in rats pretreated with hydrocortisone. Pancreatic enzyme secretion was strongly reduced in the rats subjected to acute pancreatitis, and although the drop in enzyme levels did not reach statistical significance, the values of secretion were even further reduced in the animals treated with hydrocortisone, pointing to the absence of pancreatic functionality. This effect can be attributed to enzyme storage elicited by previous hydrocortisone administration; activated intracellularly, these enzymes could aggravate the pathology. Administration of the cholecystokinin octapeptide (CCK-8) (10 micrograms/kg/day) during the development of acute pancreatitis in animals pretreated with hydrocortisone substantially improved the general state of the animals' pancreases. There was a significant decrease in serum amylase, pancreatic edema and haematocrit levels in rats injected with CCK, which was accompanied by an increase in pancreatic functionality. Conversely, the administration of L-364,718 (0.1 mg/kg/day), a CCK antagonist, did not improve pancreatic functionality and did not appreciably affect the general state of the organ. It is concluded that in rats with storage levels increased by hydrocortisone administration that are subjected to acute pancreatitis, the secretagogue effect of CCK is more beneficial than the repose of the gland induced by L-364,718.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1992

Pharmacological studies on CCKB receptors in guinea pig synaptoneurosomes.

Preliminary studies on CCK receptors in the central nervous system were carried out on guinea pig cerebral cortical synaptoneurosome preparations. In binding assays, the range of affinity of CCK-8, Boc-[Nle28,Nle31]CCK-7, a potent CCK analog, Boc-[Leu31]CCK-4 and of the two benzodiazepine CCK receptor antagonists L-365,260 and MK-329, is in agreement with the presence of CCKB receptors on this model. The effects of Boc-[Nle28,Nle31]CCK-7 on inositol phosphates, cAMP accumulation and 45Ca2+ efflux were investigated. Neither inositol phosphate nor cAMP accumulations could be observed. On the other hand, evidence of Boc-[Nle28,Nle31]CCK-7-, CCK-8- and Boc-[Leu31]CCK-4-induced 45Ca2+ efflux was found in a dose-dependent manner. The CCKB-selective receptor antagonist L-365,260 and, with a weaker efficiency, the CCKA-selective receptor antagonist MK-329, are able to block a maximal effect of Boc-[Nle28,Nle31]CCK-7-induced 45Ca2+ efflux, suggesting that CCKB receptors may regulate calcium ion mobilization.

Animals↗
PubMed1993

Cholecystokinin increases intracellular Ca2+ concentration in the Human JURKAT T Lymphocyte cell line.

We have recently demonstrated the presence of specific high-affinity cholecystokinin binding sites of the central type on the Human JURKAT T Lymphocyte Cell line. In this paper, changes in intracellular Ca2+ concentration ([Ca2+]i) in response to CCK (cholecystokinin) peptides were measured in the Human JURKAT T Lymphocyte Cell line by fura-2 fluorometry. CCK-8 (the C-terminal octapeptide of CCK), the potent CCK analog Boc-[Nle28,31]CCK-7, stimulated ([Ca2+]i) mobilization in a dose-dependent manner in cells preloaded with fura-2 AM with an EC50 of 2.4 +/- 1 nM and 8 +/- 2 nM, respectively. The selective CCKB receptor agonists, namely Boc-Trp-Nle-Asp-Phe-NH2 and the cyclic analog JMV320, [formula: see text], were also potent in stimulating mobilization of [Ca2+]i with an EC50 of 32 +/- 10 nM and 25 +/- 10 nM, respectively. Compound JMV180, Boc-Tyr(SO3H)-Nle-Trp-Nle-Asp-2-phenylethyl ester, did not stimulate [Ca2+]i but inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a dose-dependent manner with an IC50 of 10 +/- 2 nM. The selective non-peptide CCKB receptor antagonist L-365,260 was more potent than the selective CCKA receptor antagonist MK-329 in inhibiting the [Ca2+]i mobilization elicited by 10 nM CCK-8 with IC50 values of 20 +/- 8 nM and 400 +/- 100 nM, respectively. These data indicated that CCK-8 and potent CCK analogs induced [Ca2+]i mobilization in the Human JURKAT T cell line through the CCKB/gastrin receptor type.

Amino Acid Sequence↗
PubMed1994

Characterization of YM022: its CCKB/gastrin receptor binding profile and antagonism to CCK-8-induced Ca2+ mobilization.

We investigated the antagonistic activity of (R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl) urea (YM022), a benzodiazepine derivative, at CCKB/gastrin receptors. This compound potently inhibited [125I]CCK-8 binding to rat brain CCKB/gastrin receptors with a Ki value of 0.26 nM, but it showed weak affinity for rat pancreas CCKA receptors (Ki = 270 nM). Selectivity for CCKB/gastrin receptors was 1000-fold greater than that for CCKA receptors. Changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to CCK-8 were measured in a rat anterior pituitary cell line GH3 by fura-2 fluorometry. CCK-8 (1-100 nM) dose-dependently increased [Ca2+]i in these cells, whereas YM022 had no effect on baseline [Ca2+]i even at the highest concentration of 100 nM. YM022 inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a concentration-dependent manner with an IC50 value of 4 nM. In conclusion, YM022 is an extremely potent and highly selective antagonist of CCKB/gastrin receptors. This compound is therefore useful for studying the physiological and pharmacological roles of CCKB/gastrin receptors.

Animals↗
PubMed1994

Gastrin13 and the C-terminal octapeptide of cholecystokinin are differently coupled to G-proteins in guinea-pig brain membranes.

In the course of our study concerning gastrin and cholecystokinin (CCK) receptors, we synthesized and characterized a labelled gastrin ligand, [125I]BH[Leu15]gastrin-(5-17) (3-(3-[125I]iodo-4-hydroxyphenyl)propionyl[Leu15]gastrin-(5-17)). On isolated canine fundic mucosal cells and human Jurkat lymphoblastic cell line, known to express CCKB/gastrin receptors, the binding experiments performed indicate that [125I]BH[Leu15]gastrin-(5-17) provides a convenient biologically active ligand for cholecystokinin/gastrin receptor studies. We showed in this study that, on guinea-pig brain membranes known to possess CCKB and CCKA receptors, [125I]BH[Leu15]gastrin-(5-17) binds to a single class of high-affinity binding sites in a saturable and specific manner. [125I]BH[Leu15]gastrin-(5-17) interacts with guinea-pig brain membranes with a maximal binding capacity that is about three-fold lower than that of [125I]BHCCK8 (CCK8, the C-terminal octapeptide of cholecystokinin). The apparent affinities of CCK analogues and selective CCK receptor antagonists L-365,260 and MK-329 for the sites labelled by both probes were in accordance with a CCKB-like profile. Association-dissociation kinetics of [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8 were performed and compared. They showed that [125I]BHCCK8 equilibrated more slowly than [125I]BH[Leu15]gastrin-(5-17). The effects of pH, monovalent and divalent cations on binding of both probes were investigated. The results obtained did not indicate strong differences between [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8 binding. Binding experiments in the presence of stable analogues of GTP showed a different behavior between [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8. GTP gamma S strongly decreased [125I]BH[Leu15]gastrin-(5-17) binding whereas it weakly affected [125I]BHCCK8 binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of CCK and its antagonists on gastric emptying.

Cholecystokinin (CCK) belongs to the group of substances known as brain-gut peptides: it functions both as a neuropeptide and a gut hormone. The peptide and its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart caerulein) significantly delay emptying of gastric contents in both animals and humans. The fact that CCK, in doses mimicking postprandial plasma levels, strongly affects emptying rate suggests the peptide to be a physiologic regulator of gastric emptying. Unfortunately, clear definition of the role of CCK in the physiology of gastric motor activity has long been hampered by the lack of specific and potent non-peptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and examination of its putative role in certain diseases. This paper summarizes the available data concerning the effect of CCK and its antagonists on gastric emptying. The use of selective CCK-antagonists has allowed to establish that the gastric motor effect of the peptide is direct and mediated through the stimulation of CCK-A receptors. As a consequence, CCK-A antagonism results in acceleration of emptying rate under certain experimental and clinical conditions. This peculiar pharmacologic effect of CCK-A antagonists, which could be useful in the treatment of functional dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux disease (where patients often display a delayed emptying rate of solid food) needs to be further investigated, in order to fully explore their potential as gastrokinetic drugs.

Animals↗
PubMed2004

Cholecystokinin and prostaglandins inhibit responses of vagal afferent activity to systemic administration of nicotine in anesthetized rats.

Systemic administration of nicotine suppresses food intake. Since gastric vagal afferents convey satiation signals to the hypothalamus in response to cholecystokinin, we investigated the possibility that nicotine increases afferent activity of the gastric vagal nerves by stimulating release of cholecystokinin. Furthermore, involvement of prostaglandins in the responses of gastric vagal afferents to nicotine was also investigated because prostaglandins stimulate gastric vagal afferent activity. Experiments were performed in urethane-anesthetized rats. Intravenous administration of 300 microg/kg but not 3 or 30 microg/kg nicotine produced biphasic increases in afferent activity. The maximum of the first increase was reached within 1 min, while that of the second increase was reached 10-15 min after nicotine injection. Pretreatment with MK-329, a type A cholecystokinin receptor antagonist, significantly reduced the first increase, without influencing the second increase. Pretreatment with indomethacin, a cyclooxygenase inhibitor, further reduced the first increase and abolished the second increase. These results suggest that nicotine can exert its anorexic effect via an increase in gastric vagal afferent activity which is caused by enhanced release of both cholecystokinin and prostaglandins.

Anesthesia↗
PubMed1996

Bile-pancreatic juice replacement not cholinergic- and cholecystokinin-receptor blockade reverses acinar cell hyperstimulation after bile-pancreatic duct ligation.

BACKGROUND: Acinar cell inhibitors (eg, atropine) fail to ameliorate clinical and experimental acute pancreatitis. We hypothesized that amelioration of pancreatic acinar cell hyperstimulation after bile and pancreatic duct ligation is better with gut replacement of bile and pancreatic juice than with cholinergic- and cholecystokinin (CCK)-receptor blockade. METHODS: Using acinar cell amylase activity as an index of hyperstimulation, we studied 63 rats in two sets of experiments. Bile-pancreatic juice exclusion from gut--without (set one) and with (set two) bile and pancreatic duct obstruction--was treated with atropine and CCK-receptor antagonist L-364,718, or with enteral replacement of bile-pancreatic juice. RESULTS: In the set one experiment, acinar cell hyperstimulation after bile-pancreatic juice exclusion was reversed by combined L-364,718 and atropine pretreatment. In set two, acinar cell hyperstimulation after bile and pancreatic duct ligation was reversed by enteral bile and pancreatic juice replacement, but not by combined L-364,718 and atropine pretreatment. CONCLUSIONS: According to this experimental corollary of early gallstone impaction, prevention of acinar cell hyperstimulation after duct occlusion should be aimed at the source of the response to bile-pancreatic juice exclusion, namely, the gut, rather than at the target of the response, the pancreatic acinar cell.

Amylases↗
PubMed1997

Cholecystokinin regulates glycoprotein membrane composition of rat pancreatic zymogen granules.

Lectin-binding studies were performed on rat pancreatic zymogen granules to investigate the alterations in the carbohydrate membrane composition under both chronic CCK stimulation and long-term CCK blockade for 3, 7 and 15 days. By flow cytometry using FITC-WGA--which specifically binds to N-acetylglucosamine and sialic acid--we measured the amount of WGA molecules bound to each individual granule. Parallel studies on pancreatic secretion were also carried out. CCK treatment displayed a differential effect on two zymogen granule subpopulations (Z1 and Z2) identified by flow cytometry on the basis of their light scatter properties: no effects on Z2 zymogen granules were observed in CCK-treated rats, while Z1 granules showed a significant increase in WGA binding at day + 7 which coincides with an increase in protein secretion in response to the hormone. On the contrary, a significant decrease in the amount of WGA receptors was observed in zymogen granule membrane of both the Z1 and Z2 subsets of rats subjected to a long-term CCK blockade. Again, these changes parallel to the reduction observed in protein secretion. Our results suggest that glycoconjugates of zymogen granule membrane involved in CCK-regulated exocytosis contain N-acetylglucosamine and sialic acid residues whose quantities are regulated by CCK.

Animals↗
PubMed2000

Characterisation of the effects of SR146131, a novel non-peptide CCK(1) receptor agonist, on IMR-32 human neuroblastoma cells.

The effect of ¿2-[4-(4-chloro-2, 5-dimethoxy-phenyl)-5-[2-cyclohexyl-ethyl)-thiazol-2-ylcarbamoy l]-5, 7-dimethyl-indol-1-yl¿-acetic acid (SR146131), a novel non-peptide agonist of cholecystokinin (CCK) CCK(1) receptors, was compared to the effect of sulphated cholecystokinin octapeptide (CCK-8-S) on CCK(1) receptors of the human neuroblastoma cell line IMR-32. SR146131 inhibited [125I]CCK-8-S binding to IMR-32 cells at nanomolar concentrations. SR146131 and CCK-8-S increased intracellular free Ca(2+) levels ([Ca(2+)](i)) in the same concentration range (EC(50)=6+/-2.3 and 1.3+/-0.14 nM, respectively). Although the shape of the [Ca(2+)](i) increase induced by CCK-8-S and SR146131 was slightly different, extracellular Ca(2+) removal affected the response of both compounds to a similar degree, and the response of both compounds was essentially due to Ca(2+) release from intracellular stores. This was also confirmed by measuring the [Ca(2+)](i) response of single cells: both compounds induced [Ca(2+)](i) oscillations at subnanomolar concentrations and elicited a large peak increase in [Ca(2+)](i) at higher concentrations (EC(50)=0.5+/-0.04 and 5.7+/-1.9 nM for CCK-8-S and SR146131, respectively). Both CCK-8-S and SR146131 induced a sustained increase of phosphoinositide turnover in these cells, and acted at similar concentrations (EC(50)=2.7+/-0.7 and 6+/-3.1 nM, respectively), although the maximal effect of SR146131 was somewhat lower than the effect of CCK-8-S. These data show that SR146131 activates human CCK(1) receptors on IMR-32 cells in a manner and with a potency similar to that of CCK-8-S.

Benzodiazepinones↗
PubMed2003

The effects of a peripherally acting cholecystokinin1 receptor antagonist on food intake in rats: implications for the cholecystokinin-satiety hypothesis.

The observation that systemic administration of the peptide cholecystokinin (CCK) inhibits food intake in mammalian species has led to the hypothesis that endogenous peripheral CCK released from the small intestine during a meal acts as a satiety factor. It was predicted that if CCK does play an important role in satiety, then systemic administration of a specific CCK receptor antagonist should block the effects of the endogenous peptide released during a meal and increase food intake. The present study was undertaken to test the hypothesis by investigating the effects of the cholecystokinin(1) (CCK(1)) receptor antagonist N-alpha-3'-quinolinoyl-D-Glu-N,N-dipentylamide dicyclohexylammonium (A70104), which is unlikely to cross the blood-brain barrier, on food intake in rats. A70104 (20-200 microg/kg, i.p.) had no any significant effect on the intake of a test meal in rats under different experimental conditions. However, pretreatment of rats with A70104 (50 microg/kg, i.p.) abolished the inhibitory effects of exogenous peripheral CCK (5 microg/kg, i.p.) on food intake. The findings that A70104 had no effect on food intake when administered on its own, but abolishes the suppressant effect of exogenous peripheral CCK, suggest that endogenously released peripheral CCK does not play an important role as a satiety factor in rats.

Animals↗