Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a cotransmitter of inhibitory motor neurons of the enteric nervous system. This study examined the effect of 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (NOS), on intestinal peristalsis and muscle activity and compared 7-NI with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of NOS isoforms. Peristalsis in isolated segments of the guinea pig small intestine was triggered by a perfusion-induced rise of the intraluminal pressure. While L-NAME (10-300 micromol/l) lowered the peristaltic pressure threshold (PPT) at which propulsive muscle contractions were elicited, 7-NI (10-300 micromol/l) caused a concentration-related increase in PPT. L-Arginine (1-3 mmol/l) failed to reverse peristaltic motor depression evoked by 7-NI but annulled the L-NAME-evoked stimulation of peristalsis. Drugs which stimulated peristalsis, such as L-NAME, naloxone, apamin and suramin plus pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid counteracted the inhibitory effect of submaximally effective concentrations of 7-NI on peristalsis. 7-NI (100-300 micromol/l) inhibited circular muscle contractions evoked by cholecystokinin octapeptide, the NK(1) receptor agonist GR-73,632 and indomethacin whereas L-NAME (100-300 micromol/l) failed to inhibit any drug-evoked contraction. These data show that 7-NI, unlike L-NAME, inhibits circular muscle contractions of the gut and depresses intestinal peristalsis. It is concluded that the inhibitory motor action of 7-NI is unrelated to inhibition of neuronal NOS and arises from depression of smooth muscle activity.
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PMID:Intestinal motor depression by 7-nitroindazole through an action unrelated to nitric oxide synthase inhibition. 1057 25

The present study assessed the effect of a single subcutaneous injection of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, on the activity of spinal cholecystokinin (CCK) systems, by using electrophysiological and in situ hybridization techniques. Subcutaneous RTX at 0.3 mg/kg, but not vehicle, produced marked thermal hypoalgesia in rats on the hot plate and tail flick tests. Partial recovery from hypoalgesia occurred in some (<50%), but not all, RTX-treated rats after 2 weeks. The flexor reflex in response to activation of high threshold afferents was recorded 15-35 days after RTX- or vehicle-treatment. There was no obvious difference between RTX- and vehicle-treated rats in the baseline flexor reflex. Intravenous morphine at 1 mg/kg caused a depression of the flexor reflex in vehicle- and in RTX-treated rats. The reflex depressive effect of morphine was significantly briefer in RTX-treated, non-recovered rats than vehicle-treated rats. Furthermore, CI-988, a high affinity antagonist of CCKB receptors, caused a minor depression of the reflex in vehicle- and RTX-treated rats that had partially recovered, whereas the reflex depressive effect of CI-988 was significantly enhanced in RTX-treated, non-recovered rats. In situ hybridization showed that RTX treatment caused a marked and significant increase in the number of dorsal root ganglion (DRG) neurone profiles expressing CCKB receptor mRNA, whereas only a small increase was observed for CCKA receptor mRNA expressing neurone profiles. Significantly more DRG neurone profiles expressed CCKB receptor mRNA in RTX-treated, non-recovered rats compared to partially recovered rats. RTX-treatment did not influence the expression of CCK mRNA in DRGs. Since CCK functions as a physiological antagonist of morphine, it is suggested that RTX treatment enhances the activity of spinal CCK systems, leading to the reduced effect of morphine and increased effect of the CCKB receptor antagonist CI-988. This may mainly be due to upregulation of CCKB receptors in DRG neurones.
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PMID:Increased spinal cholecystokinin activity after systemic resiniferatoxin: electrophysiological and in situ hybridization studies. 1060 69

Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin (CCK) receptors. This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety. This double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity, enhances elevated-plus maze performance, and attenuates the acoustic startle response (ASR). In this study, the authors evaluated the effects of Gotu Kola on the ASR in humans. Subjects were randomly assigned to receive either a single 12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The results revealed that compared with placebo, Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no significant effect on self-rated mood, heart rate, or blood pressure. These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR. It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes.
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PMID:A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. 1110 41

The vagus nerve may indirectly influence thermoregulation by modulation of energy balance: its afferent fibers convey signals that represent information on feeding state, resulting in either depression or stimulation of metabolic processes. A regulated metabolic depression can be detected in the background of fasting-induced hypometabolism and hypothermia. In its development (besides humoral signals) vagally transmitted neural signals of gastrointestinal and hepatoportal origin are important. These signals are related to hunger, to decrease of mechanical/chemical stimuli from the gut, to decline of blood glucose; they alter discharge rates of vagal afferents and activity of the nucleus of the solitary tract, eliciting inhibition of metabolic rate and enhancement of food intake. In this hunger-related metabolic inhibition the nucleus of the solitary tract is in interaction with hypothalamic nuclei, that contribute to neuropeptide changes characterized by high neuropeptide Y activity (with energy-conserving type of regulation) and depressed cholecystokinin and corticotropin releasing hormone activities (with depressed energy-expenditure). In postalimentary states the hypermetabolism and hyperthermia are due to opposite changes in metabolic regulation. Satiety-related stimulatory signals of abdominal origin, transmitted via hepatic vagal afferents to the nucleus of the solitary tract, contribute to enhancement of sympathetic activity and stress-responsiveness, leading to hypermetabolism and hyperthermia. Depressed neuropeptide Y release and enhanced cholecystokinin and corticotropin releasing hormone activities participate in the central regulatory changes, and in the high energy-expenditure. The biological role of these vagal functions is not directly the regulation of body temperature, rather the regulation of energy balance and energy content in the body.
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PMID:The vagus nerve in thermoregulation and energy metabolism. 1118 24

Food intake declines throughout the life span. This physiologic anorexia of aging is caused in part by alterations of stomach-fundus compliance and release and activity of cholecystokinin. In addition, the decline in testosterone in males results in elevated leptin levels that increase the anorexia. There is also evidence that cytokines play a role in the pathogenesis of anorexia and sarcopenia, thus accelerating the development of frailty in older persons. Numerous treatable causes of anorexia and weight loss exist. Depression is the most commonly diagnosed cause of pathologic weight loss in older persons.
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PMID:Anorexia, sarcopenia, and aging. 1144 92

Infection with the bovine abomasal nematode, Ostertagia ostertagi, results in a loss of acid-secreting parietal cells and an increase in gastric pH. The effects of an experimental infection with Ostertagia and/or daily treatment with omeprazole (OMP) at 2mgkg(-1) bodyweight for four consecutive days (experiment days 24-27, inclusive) on voluntary feed intake, blood and tissue gastrin concentrations, abomasal G-cell numbers, gastric pH, and blood cholecystokinin (CCK) and pepsinogen concentrations were investigated in the calf. Ostertagia-infected calves demonstrated a significant drop in feed intake between days 24 and 27 post-infection (38%; P<0.001) and in G-cell numbers (42%; P<0.05) and significant increases in abomasal pH (P<0.001), fundic mucosal weight (99%; P<0.01), and blood gastrin (P<0.05) and pepsinogen (P<0.0001). OMP treatment of worm-free animals resulted in a significant drop in intake between days 24 and 27 (30%; P<0.001) and in G-cell numbers (17%; P<0.05) and significant increases in abomasal pH (P<0.01) and blood gastrin (P<0.001). OMP treatment of Ostertagia-infected animals with an existing hypergastrinaemia had no effect on feed intake, abomasal pH, blood gastrin or pepsinogen or abomasal G-cell numbers. Blood CCK concentrations were also unaffected by either Ostertagia infection or OMP treatment. These data suggest that: (a) the depression in feed intake associated with OMP in worm-free calves was not due to a side effect of drug treatment; (b) inappetance in Ostertagia-infected animals is closely associated with the parasite-induced hypergastrinaemia; and (c) the elevation in abomasal pH was a major factor responsible for the elevated blood gastrin concentrations seen in parasitised and OMP-treated animals.
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PMID:Effects of Ostertagia ostertagi and omeprazole treatment on feed intake and gastrin-related responses in the calf. 1198 4

Synapses exhibit different short-term plasticity patterns and this behaviour influences information processing in neuronal networks. We tested how the short-term plasticity of excitatory postsynaptic currents (EPSCs) depends on the postsynaptic cell type, identified by axonal arborizations and molecular markers in the hippocampal CA1 area. Three distinct types of short-term synaptic behaviour (facilitating, depressing and combined facilitating-depressing) were defined by fitting a dynamic neurotransmission model to the data. Approximately 75 % of the oriens-lacunosum-moleculare (O-LM) interneurones received facilitating EPSCs, but in three of 12 O-LM cells EPSCs also showed significant depression. Over 90 % of the O-LM cells were immunopositive for somatostatin and mGluR1alpha and all tested cells were decorated by strongly mGluR7a positive axon terminals. Responses in eight of 12 basket cells were described well with a model involving only depression, but the other cells displayed combined facilitating-depressing EPSCs. No apparent difference was found between the plasticity of EPSCs in cholecystokinin- or parvalbumin-containing basket cells. In oriens-bistratified cells (O-Bi), two of nine cells showed facilitating EPSCs, another two depressing, and the remaining five cells combined facilitating-depressing EPSCs. Seven of 10 cells tested for somatostatin were immunopositive, but mGluR1alpha was detectable only in two of 11 tested cells. Furthermore, most O-Bi cells projected to the CA3 area and the subiculum, as well as outside the hippocampal formation. Postsynaptic responses to action potentials recorded in vivo from a CA1 place cell were modelled, and revealed great differences between and within cell types. Our results demonstrate that the short-term plasticity of EPSCs is cell type dependent, but with significant heterogeneity within all three interneurone populations.
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PMID:Cell type dependence and variability in the short-term plasticity of EPSCs in identified mouse hippocampal interneurones. 1209 61

We have recently identified a novel polymorphic short tandem repeat (STR) in the 5' upstream region of the cholecystokinin (CCK) gene and reported its association with panic disorder. A linkage study of affective disorder showed a modest linkage signal on the short arm of chromosome 3, the location of the CCK gene. Furthermore, clinical comorbidity of depression and anxiety disorders have been documented. In the present study, we examined a possible association of the CCK STR with mood disorders. We genotyped 165 subjects with mood disorders consisting of unipolar and bipolar disorders and 253 control samples. However, no significant allelic associations were detected between the STR and either the combined mood disorders (P = 0.885), the unipolar group (P = 0.296), or the bipolar group (P = 0.605). These data suggest that the CCK promoter STR is unlikely to have a major genetic effect on the development of mood disorders in the Japanese population.
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PMID:Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population. 1211 88

The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.
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PMID:Pharmacologic therapy for the irritable bowel syndrome. 1273 51

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.
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PMID:Eating habits and appetite control in the elderly: the anorexia of aging. 1283 2


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