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)

Local injections of the tetradecapeptide somatostatin (SOM) into the brain stem region were performed in anesthetized and decerebrate rats. SOM administration (0.6-1.8 nmol) into the nucleus paragigantocellularis and the nucleus reticularis lateralis of the ventrolateral medulla oblongata induced ventilatory depression and apnea. The occurrence of apnea was dose dependent and attributed to the anesthetic depth, and it was seen within 60-240 s after injection. In anesthetized rats the apnea was seen as a termination or a continuous decrease in tidal volume while respiratory frequency remained unaltered. SOM-induced apnea was caused by depression of central inspiratory drive. SOM injections into the dorsal medulla were ineffective in eliciting apnea, although a ventilatory depression but no apnea was induced in the awake unanesthetized state. In addition to its effect on basal ventilation, SOM administration in the ventrolateral medulla resulted in a blunted ventilatory response to hypoxic and hypercapnic stimuli in anesthetized rats. We conclude that SOM has potent inhibitory effects on respiration that are specifically located in the nucleus paragigantocellularis and the nucleus reticularis lateralis.
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PMID:Local application of somatostatin in the rat ventrolateral brain medulla induces apnea. 198 70

Daily cyclosporine doses of 10 mg/kg body weight for 21 days in Wistar rats cause impairment in glucose homeostasis and changes in the amount of immunostainable hormones and in the ultrastructure of the cells of the pancreatic islets. CsA induces hyperglycemia and reduced glucose tolerance, and causes a decrease in immunoreactive insulin and an increase of somatostatin and pancreatic polypeptide (PP) immunoreactivities, leaving glucagon immunoreactivity unaffected. Ultrastructurally, different degrees of dilation of rough endoplasmic reticulum cisternae and enlargement of Golgi apparatus can be observed in B cells, together with a pronounced reduction in the number of secretory granules. Nevertheless, there were no apparent morphological changes of the other cytoplasmic organelles, suggesting that the drug, besides a depression of protein synthesis, as previously stated, also induces a substantial defect in granulogenesis, probably due to impairment in the intracellular transport of the hormone from the sites of synthesis to the secretory granules. The B cell alterations are not accompanied by any sign of B cell degeneration or death. Non-B cells did not show any of the ultrastructural changes found in B cells and were similar to those of the control rats. The above findings indicate that CsA at immunotherapeutic doses causes impairment in the secretory processes of B cells specifically. An hypothesis on the mode of action of CsA on B cells is drawn.
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PMID:Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses. 218 26

In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open-field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission.
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PMID:Comparative studies of intracerebroventricularly administered cysteamine and pantethine in different behavioral tests and on brain catecholamines in rats. 224 25

We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that depletion or somatostatin may not be the only mechanism underlying cysteamine's effect on kindling. The results also support the likelihood that PTZ kindling primarily effects neocortical rather than limbic structures.
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PMID:Pentylenetetrazole-induced kindling is prevented by prior treatment with cysteamine. 240 13

Nine patients with psoriasis vulgaris were treated for 12 weeks with somatostatin analog, octreotide acetate (SMS 201-995) 50 or 100 micrograms by subcutaneous injection every 12 hours. The purposes of the study were to determine: (1) levels of insulin, glucose, glucagon, pancreatic polypeptide (PP), and SMS 201-995 after a subcutaneous injection of SMS 201-995 and ingestion of a standardized meal; (2) nocturnal (0200 h) thyroid stimulating hormone (TSH) levels before, during, and after treatment; and (3) the pharmacokinetics of SMS 201-995. Insulin peaks at 30 minutes were blunted from 65.8 +/- 11.0 mu U/mL without treatment to 26.7 +/- 8.6 mu U/mL and 7.7 +/- 2.0 mu U/mL after the 50- and 100-micrograms doses, respectively. Glucagon levels remained constant during the meal and were not affected by the 50-micrograms dose. Mean glucose levels were significantly elevated during insulin suppression. PP was also rapidly suppressed by SMS 201-995 and remained so for 4 hours after the injection. Nocturnal TSH was blunted after 12 weeks of treatment (P less than or equal to .05). T4 and T3 resin uptake showed no depression, and patients remained clinically euthyroid. The plasma peak of SMS 210-995 occurred 30 minutes postinjection and half-life was longer than 2 hours. After chronic administration of SMS 201-995, insulin was suppressed with resultant mild carbohydrate intolerance that persisted throughout the treatment course.
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PMID:Treatment of psoriasis with chronic subcutaneous administration of somatostatin analog 201-995 (sandostatin). II. Effect on pancreatic and thyroid hormone. 240 89

Chronically implanted rats were injected either with somatostatin (SST) lumbar intrathecally (i.t.) (100 micrograms, n = 5), into the fourth ventricle (3 micrograms, n = 5; 10 micrograms, n = 6; 30 micrograms, n = 5) or into the lateral ventricle (10 micrograms, n = 6; 30 micrograms, n = 6), or received an injection of the substance P (SP) analogue, [D-Pro2, D-Trp7,9]SP into the fourth ventricle (0.3 micrograms, n = 2; 1 micrograms, n = 4; 3 micrograms, n = 4; 10 micrograms, n = 1) or lateral ventricle (3 micrograms, n = 3). A dose-dependent EEG depressant effect was observed following fourth and lateral ventricular injections of SST and of the SP analogue. Acute death due to respiratory depression was observed following i.t. and fourth ventricular injection of SST, and fourth ventricular injection of the SP analogue. Prominent motor behavior (barrel rotation, circling, cranial stereotypies) was observed, without signs of EEG seizure activity, following intraventricular injection of both drugs. Present findings indicate neurotoxic effects of SST and SP analogue at the cerebral level.
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PMID:Electroencephalographic and behavioral assessment of intracerebroventricular somatostatin and a substance P analogue. 247 57

The effect of gamma-aminobutyric acid (GABA) on basal and bombesin (BBS)-stimulated release of somatostatin (SLI) and gastrin from isolated perfused rat stomach was examined. In the control study, BBS at a dose of 10 nM significantly stimulated release of SLI and gastrin. Infusion of GABA (1-1000 nM) caused a depression of SLI release induced by BBS (10 nM) in a dose-dependent fashion. However, at doses used in this study GABA had no effect on either basal level of SLI and gastrin or BBS-elicited gastrin release. These results indicate that GABA can specifically modulate BBS-induced SLI release from rat stomach.
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PMID:Effect of gamma-aminobutyric acid on bombesin-evoked release of somatostatin and gastrin from isolated rat stomach. 256 10

In vitro assessment was made of the hormone-release capability of splenic pancreatic tissue 16 days after adult chickens had 99% of the pancreatic mass surgically removed. The objective of this study was to evaluate if the enlargement of the splenic lobe remnant after 99% pancreatectomy was attended by alterations in the responsivity of hormone release and, if so, were such changes reflective of all pancreatic hormones. After a 24-hr fast, splenic lobe tissue was obtained from young adult chickens on Postoperative Day 16, diced into 18-22 mg cubes, and incubated in vitro in media containing varying amounts of glucose with or without added somatostatin (SRIF). At 15-min intervals, the tissue cubes were transferred to fresh media and samples of each medium measured for insulin, glucagon, and APP. Viability of the tissue after 75 min was tested by tissue response to added 5 mM phenylalanine. The results obtained indicated that while total content of all four hormones (including SRIF) increased with tissue enlargement, the concentration of each decreased significantly except for SRIF, which remained at control levels. Further, the sensitivity of the B-cell in releasing insulin when confronted by a glucose challenge was not altered by previous pancreatectomy, while that of glucagon release from the A-cell was depressed. A-cell responsivity to SRIF does not appear to be adversely affected by previous 99% pancreatectomy. APP release was least affected by SRIF addition to the media, although depression by high glucose occurred. It is concluded that differential alterations occur in chicken pancreatic hormone-releasing cells as a result of 99% pancreatectomy. The efficacy in maintaining low, but still adequate, plasma I/G molar ratios (reported earlier) by the splenic remnant tissue either reflects a remarkable functional readjustment to surgical removal of 99% of the pancreatic mass in chickens or, alternatively, suggests the existence of extrapancreatic sources of insulin and glucagon, but not APP.
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PMID:In vitro release of pancreatic hormones following 99% pancreatectomy in the chicken. 256 76

The mechanism of action of aspirin as an analgesic is an inhibition of biosynthesis of prostaglandins. Thus the site of action has been believed to be peripheral. However, when aspirin is injected intra- thecally, it produces an analgesic effect. Aspirin has a membrane-stabilizing effect and it is used locally for the treatment of post- herpetic neuralgia. Epidural opioids are frequently used for the management of post-operative pain or cancer pain. Pharmacokinetic studies have shown that delayed respiratory depression results from migration of morphine in the cerebrospinal fluid to the brain. Peak concentrations of morphine near the brain stem occur about 3 hours after lumbar epidural injection, whereas lipophilic opioids such as meperidine, peak concentration occur within 30 to 60 minutes. The clearance from cerebrospinal fluid of lipophilic opioids is more rapid than that of morphine. Besides opioids, alpha 2 receptor agonists such as clonidine also have analgesic action when administered into the epidural space. Somatostatin is one of many neuropeptides found in the spinal cord. It has dual action: a mediation of thermal nociception and a general antinociceptive action. When somatostatin is administered intrathecally or epidurally, it produces analgesic effect and its efficacy appears to be equal to that of morphine.
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PMID:[Remarks on some analgesics used in the pain clinic]. 256 60

The extent and distribution of biochemical abnormalities thought to reflect disorders of subpopulations of neurons have been determined in the cerebral cortex from brains of patients with Alzheimer-type dementia and depressive illness who died of natural causes. In dementia, loss of gray matter from areas of the parietal and temporal lobes is most obvious. In depression, these areas are not affected, but the pars opercularis and temporal pole are smaller than in controls. Results expressed per unit mass of total protein indicate selective reductions in both disorders of serotonin 2 recognition sites in all areas examined and of somatostatin content in only the temporal pole of the six areas examined. In dementia alone a selective loss was found of somatostatin content of the superior parietal lobule and of serotonin 1A sites and choline acetyltransferase activity in all areas examined. Results for depression expressed per entire area indicate additionally reduced somatostatin content and serotonin 1A sites in the pars opercularis and serotonin 1A sites in the temporal pole. These multiple analyses performed on each sample provide further support for a prominent disorder of pyramidal neurons in dementia as well as more evidence for alterations in cortical neurons in depression, either as a result of the disease itself or its treatment.
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PMID:Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. 257 63


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