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)

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.
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PMID:Cerebrospinal fluid neuropeptides in dementia. 148 50

The etiology of Alzheimer's disease (AD) is still unknown, and a definitive diagnosis of the disease can be determined only at autopsy or by brain biopsy. AD can be characterized by various structural changes, including cerebral cortical atrophy, neuronal loss, neuritic plaques, and neurofibrillary tangles. The primary defect involves reduced activity of choline acetyltransferase. Neurotransmitters, such as norepinephrine, serotonin, dopamine, and somatostatin, are also compromised. Treatment of AD requires maintenance of a consistent lifestyle and environment for the patient, as well as counseling and support for the patient's family. Medications, which have been effective in some patients, are primarily used to improve cognitive function and modify behavior. Cognitive medications such as tacrine hydrochloride and physostigmine have proven beneficial in some patients, while behavioral medications have been effective in the treatment of depression, aggression, agitation, and anxiety associated with AD. However, the side effect profile of each medication and its probable overall benefit to the individual patient should be evaluated before beginning therapy. Continued research in patients with AD is required to identify medications that will consistently ameliorate the memory loss associated with the disease.
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PMID:Current concepts in the treatment of Alzheimer's disease. 157 22

Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides. Stimulation of these receptors by their appropriate ligands such as endogenous (e.g. enkephalis, endorphins) or exogenous opioids, clonidine, serotonin, somatostatin inhibits the release of excitatory neurotransmitters and relieves pain. There are at least 3 different opioid receptors, called mu-, kappa- and delta-receptors in the spinal cord. These can be differentiated from one another by their specific affinity toward different endogenous or exogenous opioids and the pure narcotic antagonist, naloxone. It appears that the nociferous impulses transmitted by parallel pathways equipped with different inhibitory receptors have to be integrated to produce pain sensation and partial inhibition of transmission in different pathways or complete inhibition in one of the pathways may relieve pain. In recent years the concept of "selective spinal analgesia" has been applied clinically for the relief of postoperative, obstetrical and chronic pain. At first it was expected that the intrathecal or peridural administration of morphine will produce analgesia without the side effects of systemically administered morphine. It soon became evident, however, that intrathecally and peridurally administered morphine after several hours of delay reaches the fourth ventricle and by stimulating mu-receptors may cause respiratory depression and other undesired effects (e.g. nausea, vomiting, pruritus). Several different approaches are being investigated for the production of selective spinal analgesia without side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha 2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.
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PMID:Pain control with intrathecally and peridurally administered opioids and other drugs. 168 73

The role of serotoninergic pathways in the regulation of growth hormone secretion in the sheep has been investigated. Both peripheral and central routes of administration of serotonin agonists and antagonists have been used. Intravenous administration of the serotonin agonist, buspirone, at 1.2 mg/kg/h lowered plasma GH levels (P less than 0.001) but at 0.21 mg/kg/h there was no significant decrease. Intracerebroventricular (icv) administration of serotonin itself also depressed GH levels (P less than 0.01). The serotonin antagonist, cyproheptadine, failed to affect GH concentrations when given either intravenously (0.25 mg/kg/h) or intracerebroventricularly (4 mg). Neither serotonin nor cyproheptadine had any significant effect on plasma glucose or cortisol levels when administered icv. The possible role of somatostatin in mediating the serotonin associated decrease in GH was investigated by concurrent administration of serotonin and a specific, potent anti-somatostatin serum into a cerebral ventricle. This treatment also resulted in a marked, sustained depression in GH (P less than 0.001). These data suggest that serotonin can inhibit release of GH from the pituitary in sheep and that this is independent of hypothalamic somatostatin.
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PMID:Neuroendocrine regulation of growth hormone secretion in sheep. III. Serotoninergic systems. 168 45

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.
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PMID:CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression. 171 76

The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly (icv) or intravenously (iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 micrograms or 200 micrograms of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P less than 0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of antisomatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 micrograms icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P less than 0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.
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PMID:Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin. 178 2

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.
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PMID:Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats. 196 62

The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was investigated using a submerged slice preparation and intracellular recording techniques. Somatostatin-14 applied by superfusion or by pressure ejection from micropipettes predominantly inhibited the intracellularly recorded fast inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP and fIPSP amplitude occurred at low concentrations of peptide, in the absence of appreciable changes in the passive-membrane properties of postsynaptic neurons, and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor responses underlying the fIPSP and LHP were investigated by applying baclofen, a selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB receptor stimulation were significantly decreased during superfusion of SS-14. Tetrodotoxin applied by superfusion blocked electrically evoked synaptic potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine-induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also occurred but less frequently and consistently than the depressant action. Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate appeared unaltered by bath-applied SS-14. These findings suggest a novel postsynaptic action of SS-14 leading to depression of synaptic responses mediated by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may participate in modulation of feedforward and/or feedback inhibitory mechanisms coordinating DLSN function in the septo-hippocampal system.
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PMID:Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral septal nucleus. 197 66

The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.
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PMID:Role of gastrin in bombesin-stimulated somatostatin release. 197 61

The synthesis of the cytoskeletal protein actin exhibits, in the rat hypothalamus, a diurnal variation with maxima during morning hours. The objective of the present study was to assess whether melatonin injection could affect the in vitro incorporation of 35S-methionine into actin, as well as the levels of actin mRNA, in the hypothalamus of adult male rats treated either acutely or chronically with the hormone at 10:00 or 18:00. Injection of 100 micrograms/kg of melatonin for ten days at either time induced a significant depression in the incorporation of 35S-methionine into a 43 kDa protein with the electrophoretic mobility of actin. The specific activity of total soluble proteins after labeled methionine incubations decreased only after evening melatonin administration (100 micrograms/kg, ten days). Hypothalamic actin mRNA levels, quantitated by dot-blot analysis, decreased only after the injection of 100 micrograms/kg melatonin for ten days at 10:00. Neither a 10-micrograms/kg dose of melatonin, nor a single injection of 100 micrograms/kg melatonin, caused any significant change in the parameters examined. Melatonin (100 micrograms/kg for ten days) did not modify hypothalamic somatostatin or H-Ras mRNA concentration. These results suggest the existence of an inhibitory effect of melatonin on hypothalamic actin synthesis.
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PMID:Time-dependent effect of melatonin on actin mRNA levels and incorporation of 35S-methionine into actin and proteins by the rat hypothalamus. 197 1


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