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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the in vitro hippocampal slice, novel interactions of a beta-adrenergic agonist (l-isoproterenol) and neuropeptide (cholecystokinin 8-S) differentially produce long-lasting modifications in the dentate gyrus. When co-applied, a low concentration of l-isoproterenol (50-75 nM) and cholecystokinin 8-S (1.0 microM) produce long-lasting depression of evoked action potentials (i.e., population spikes). In contrast, the same concentration of l-isoproterenol followed by a 30-min wash with artificial cerebrospinal fluid and application of cholecystokinin 8-S produces long-lasting potentiation of evoked action potentials. In neither condition are there corresponding modifications of excitatory post-synaptic potentials. These results indicate that l-isoproterenol and cholecystokinin 8-S temporally interact to differentially produce depression or potentiation of granule cell-activation In contrast to long-lasting modifications produced by continuous application of 1.0 microM l-iso-proterenol, in which both evoked action potentials and excitatory post-synaptic potentials are affected, the present novel paradigm may modify an extra-synaptic locus.
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PMID:Long-lasting potentiation and depression by novel isoproterenol and cholecystokinin 8-S interactions in the dentate gyrus. 781 44

1. The 5-HT4 receptor has only recently been identified but has yet to be cloned. This paper describes the pharmacology of a potent and selective 5-HT4 receptor antagonist, GR113808, which will be useful in the further characterization of this receptor. 2. On the guinea-pig ascending colon, GR113808 (1 nM-0.1 microM) behaved as an antagonist of 5-hydroxytryptamine (5-HT)-induced contraction, producing rightward displacements of the concentration-effect curve to 5-HT and a concentration-related depression of the maximum effect. However, the compound had no effect on cholecystokinin (CCK-8)-induced contraction in concentrations up to 1 microM. 3. In the guinea-pig colon preparation, onset and offset of the antagonism by GR113808 of 5-HT-induced contraction was examined. Incubation of the tissues for either 15 min, 30 min or 60 min produced similar rightward displacements of the concentration-effect curves to 5-HT, with no increase in the degree of depression of the maxima with increasing time of incubation. Experiments examining offset of antagonism (0.01 microM) demonstrated that washout for 30 min was required to reverse fully the effects of the antagonist. 4. Potency estimates in the colon for GR113808 were made by determining approximate pA2 values (30 min) using the Gaddum equation. The values obtained were 9.2, 9.7 and 9.2 when tested against the agonists 5-HT, 5-methoxytryptamine and R,S-zacopride respectively. 5. On the carbachol-contracted tunica muscularis mucosae preparation of the rat thoracic oesophagus, GR113808 behaved as an antagonist of 5-HT-induced relaxation, producing no reduction in maximum response. Analysis of these data yielded a pA2 of 9.3. GR1 13808 also antagonised the relaxant effects of 5-methoxytryptamine (pA2 = 9.0) and R,S-zacopride (pA2 = 9.4). The compound had no effect on isoprenaline-induced relaxation of the carbachol-contracted oesophagus at a concentration of 1 MicroM.6. In tests of selectivity, GR113808 had only low affinity for 5-HT3 receptors (pKi = 6.0) and had no functional activity at either 5-HT2 or 5-HT1-like receptors on vascular smooth muscle preparations. In a range of binding assays, GRi 13808 was shown to have no appreciable affinity for any other receptor type investigated.7. In the anaesthetized piglet, GRI13808 was a potent antagonist of 5-methoxytryptamine-induced tachycardia (mean DRo = 97.2 microg kg-1 h-1). The compound was ineffective against isoprenaline-induced tachycardia.8. The present results are discussed in comparison with those for existing antagonists at the 5-HT4receptor. The results of this study indicate that GRI13808 will be a valuable antagonist for studying 5-HT4 receptor mechanisms in vitro and in vivo and validate its use as a radioligand for determining 5-HT4 receptor distribution.
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PMID:GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. 801 15

Insulin and glucagon metabolism in the pancreas with obstructive jaundice caused by complete ligation of the common bile duct and in the cholestatic liver caused by hepatic duct ligation was evaluated experimentally using dogs. The isolated perfused pancreas in obstructive jaundiced dogs, which showed a low insulin response in the peripheral blood after intravenous glucose administration, revealed depression of insulin production and no change of glucagon production in response to cholecystokinin octapeptide. The extraction of insulin in the cholestatic lobe of the liver was decreased compared with that in the noncholestatic lobe. The extraction of glucagon, on the other hand, in the cholestatic lobe and in the noncholestatic lobe showed no significant difference. So the imbalance of glucose metabolism in obstructive jaundice does not depend on the enhanced extraction of insulin in the liver, but on the depression of insulin production in the pancreas.
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PMID:Metabolism of insulin and glucagon in liver and pancreas in dogs with obstructive jaundice. 846 Jan 1

1. Virginiamycin, a macrolide reported to bind selectively to CCKB/gastrin receptors has been studied in a functional test, namely cholecystokinin-induced contraction of guinea-pig ileum myenteric plexus (LMMP). 2. Virginiamycin (1-10 microM) antagonized the selective CCKB agonist cholecystokinin tetrapeptide (CCK-4). The antagonism appeared not to be competitive as the highest concentration (10 microM) caused a reduction of its maximal effect. An apparent pA2 of 6.64 +/- 0.06 (s.e.) could be estimated if this depression was ignored. The selective CCKB antagonist, L-365,260 (0.01-0.3 microM) antagonized competitively the CCK-4 induced contraction and a pKB of 8.60 +/- 0.16 (s.e.) was estimated. 3. The combined dose-ratio analysis for virginiamycin, tested at 3 and 10 microM in association with 0.03 and 0.1 microM L-365,260, respectively, resulted in observed log dose-ratios of 1.39 and 1.53. That was consistent with both antagonists acting on the same receptor in LMMP. 4. These data, represent the first evidence of the antagonism of virginiamycin in a functional assay and they support the hypothesis of homogeneity between CCKB receptors in the CNS and in peripheral tissues.
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PMID:Analysis of the CCKB receptor antagonism of virginiamycin in guinea-pig ileum longitudinal myenteric plexus. 848 26

Cholecystokinin octapeptide (CCK-8) is reported to antagonize the analgesic effect produced by mu- and kappa- but not delta-opioid agonist in spinal cord. However, the mechanisms of interaction remain obscure. In the present study, whole-cell patch-clamp recording was performed on acutely isolated rat dorsal root ganglion (DRG) neurons to evaluate the effects of the highly specific mu-opioid agonist ohmefentanyl and the delta-opioid agonist DPDPE on voltage-gated calcium channels and the possible interaction between CCK-8 receptor and mu- or delta-opioid receptor. The results indicated that ohmefentanyl, but not DPDPE, can suppress the voltage-gated calcium currents elicited in DRG neurons, an effect readily reversed by naloxone or by the antiopioid peptide CCK-8. The effect of CCK-8 can in turn be abolished by the CCK-B receptor antagonist L365,260. CCK-8 used by itself has no enhancing effect, but rather a depressant effect, on calcium currents. However, used simultaneously with ohmefentanyl, CCK-8 shows a clear-cut reversal of depression of the mu-opioid. We conclude that the depressant effect produced by mu-opioid on voltage-gated calcium current in DRG neurons can be antagonized by CCK-8 through CCK-B receptor located in the same neuron. The delta-opioid DPDPE has no direct effect on the voltage-gated calcium current in DRG neurons.
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PMID:Cholecystokinin octapeptide reverses mu-opioid-receptor-mediated inhibition of calcium current in rat dorsal root ganglion neurons. 853 Oct 95

Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the mesolimbic system, where it may facilitate the function of DA through the CCKA receptor subtype. DA has been implicated in the acquisition of conditioned incentive learning, raising the possibility of a role for endogenous CCK in this learning process. This hypothesis was tested using two complementary behavioral paradigms. Experiment 1 examined the effects of systemic administration of the CCKA receptor selective antagonist, devazepide (0, 0.001, 0.01, 0.1 mg/kg), on the acquisition of conditioned reward. Two novel levers were presented to drug-free animals in a test session; depression of the conditioned reward (CR) lever produced a light-tone stimulus previously paired with food availability while depression of the non-CR lever produced no programmed consequence. Animals receiving vehicle pretreatment in the food-CS conditioning sessions responded more frequently on the CR lever during the test session. However, pre-treatment with devazepide (0.1 mg/kg but not 0.001 or 0.01 mg/kg) in the conditioning sessions blocked the acquisition of conditioned reward. In contrast, experiment 2 showed that the development of conditioned reward was not affected by similar administration of the CCKB selective antagonist, L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg). The possibilities that devazepide (0.1 mg/kg) impaired the development of conditioned reward by decreasing the amount of food consumed or by inducing a conditioned taste aversion to the food were ruled out in experiments 3 and 4. The effects of devazepide on the acquisition of conditioned activity induced by amphetamine were assessed in experiment 5. During four conditioning sessions, rats received devazepide (0, 0.001, 0.01, 0.1 or 1.0 mg/kg) treatment prior to amphetamine-environment pairings. The conditioned activity effect was demonstrated if on the subsequent drug-free test day the environment alone elicited increased locomotion. Devazepide (0.1 or 1.0 mg/kg) attenuated the development of conditioned activity. Together, these results provide converging evidence that intact CCKA function may be necessary for the development of conditioned incentive learning.
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PMID:Devazepide, a CCKA receptor antagonist, impairs the acquisition of conditioned reward and conditioned activity. 874 36

The relationship between personality, as measured by selected clinical scales of the Minnesota Multiphasic Personality Inventory (MMPI) (Hypochondriasis, Depression, Hysteria, Psychasthenia, Social Introversion, and Anxiety) and the Anxiety Sensitivity Index (ASI), and behavioral response to the panicogenic agent cholecystokinin-tetrapeptide (CCK-4) was examined in 29 patients with panic disorder with or without agoraphobia. Significant correlations were found between the MMPI Social Introversion scale and somatic, cognitive, and affective response to CCK-4. Both the MMPI Anxiety scale and the ASI correlated significantly with cognitive response to CCK-4, but not with somatic or affective response. None of the other selected MMPI clinical scales correlated with response to CCK-4. Multiple regression analyses identified the MMPI Social Introversion scale as the best predictor of all three indices of panic-anxiety induced by CCK-4. The results suggest that the relationship between neurotic introversion and sensitivity to CCK requires closer scrutiny.
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PMID:Influence of personality on behavioral response to cholecystokinin-tetrapeptide in patients with panic disorder. 877 10

To investigate changes in motility of the extrahepatic biliary system associated with emesis, we measured the volume of the gallbladder and flow resistance through the sphincter of Oddi, as well as antral and duodenal contractilities before and during retching in decerebrate paralyzed dogs. Motilities of the gallbladder, sphincter of Oddi, duodenum and antrum were enhanced with most episodes of fictive retching elicited by stimulation of the central part of the severed dorsal, as well as the ventral trunk of the thoracic vagus nerve. These enhanced motilities persisted until the end of retching. Motilities of the sphincter of Oddi and duodenum were sometimes transiently depressed at the beginning of retching. This depression in the sphincter continued for only 13 +/- 1.0 s, while the gallbladder contraction continued for 65 +/- 3.4 s. Motilities were rarely enhanced by vagal stimulation when retching was not elicited. These changes in motilities were abolished by bilateral vagotomy. The serum gastrin level was increased just after and 10 min after retching only when the ventral vagal trunk remained intact, while the plasma cholecystokinin level was not changed with retching. These results suggest that bile evacuation is interrupted with emesis despite contraction of the gallbladder during retching, since the sphincter of Oddi also contracts simultaneously.
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PMID:Changes in extrahepatic biliary motilities with emesis in dogs. 878 85

Anorexia and weight loss are common findings in older persons. Over a life-time, normal persons decrease their food intake to counterbalance the decrease in physical activity and resting metabolic rate that occurs with aging. This physiological anorexia of aging increases the propensity to develop pathological anorexia and weight loss when an older person develops either a medical or psychological illness. The physiological anorexia of aging is due to a decreased opioid (dynorphin) feeding drive and an increase in the satiating effect of the gastrointestinal hormone, cholecystokinin. Nitric oxide deficiency may play a role in the early satiation commonly seen in older persons. A variety of social, psychological and medical conditions can lead to pathological anorexia. Depression is the most common cause of weight loss and anorexia in older persons. A number of conditions such as cancer and rheumatoid arthritis produce their anorectic and wasting effects by releasing cytokines. An idiopathic pathological senile anorexia has been characterised which also appears to be a cytokine-dependent syndrome. Early screening for malnutrition is a cornerstone of the management of anorexia; the Mini Nutritional Assessment is a well validated screening tool available for this purpose. Aggressive use of caloric supplements, enteral tube feeding and peripheral parenteral nutrition all have a role in the early management of anorexia. Numerous drugs (growth hormone, megestrol, cyproheptadine, tetrahydrocannabinol, anabolic steroids, prokinetic agents and antidepressants) have been utilised to treat the anorexia of aging with varying success.
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PMID:Anorexia in older persons: epidemiology and optimal treatment. 884 87

High fat diets often decrease feed intake in dairy cows; however, mechanisms underlying fat-induced depression of feed intake are yet to be established. The postulate that high fat diets decrease feed intake by increasing concentrations of lipid metabolites or satiety hormones in blood was tested by using eight multiparous Holstein cows in a simultaneously replicated 4 x 4 Latin-square design. Treatments were control diet with 1) no fat added, 2) 30 g/kg calcium salts of long-chain fatty acids, 3) 60 g/kg calcium salts of long-chain fatty acids, and 4) 90 g/kg calcium salts of long-chain fatty acids. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage and alfalfa hay (50:25:14:11 on a dry matter basis). Dry matter and energy intakes were decreased by inclusion of calcium salts of long-chain fatty acids >30 g/kg of total diet dry matter (P = 0.0001). Plasma nonesterified fatty acids and triglyceride concentrations were increased linearly by feeding increasing amounts of fat (P < 0.003 and P = 0.0001, respectively), whereas plasma beta-hydroxybutyrate and glucose concentrations were not influenced by supplemental fat. Fat supplementation increased postfeeding plasma cholecystokinin concentrations and linearly increased plasma pancreatic polypeptide concentrations. Highest concentrations of plasma cholecystokinin (P < 0.001) and pancreatic polypeptide (P < 0.05) were observed in cows fed the 90 g/kg fat supplement. Plasma insulin was lowered linearly by feeding fat (P = 0.0001). Increased concentrations of cholecystokinin and pancreatic polypeptide were associated with decreased intakes of feed and energy, whereas insulin may not be involved in the control of feed intake in cows fed fat.
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PMID:High fat diets increase plasma cholecystokinin and pancreatic polypeptide, and decrease plasma insulin and feed intake in lactating cows. 891 65


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