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)

1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.
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PMID:Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats. 152 79

The monosynaptic reflex (MSR), recorded extracellularly from the ventral root isolated, superfused spinal cords of neonatal rats (6-10 days post-partum), was rapidly depressed to 35-45% of control values by either cessation of superfusion (4 min stop-flow period) or by superfusion with anoxic medium (95% N2-5% CO2; 4 min). The depression was reversible, 85-115% recovery occurring after 15 min of restoration of flow or normoxic (95% O2-5% CO2) superfusion. 2-Chloroadenosine, a metabolically stable adenosine analogue, also reversibly inhibited the MSR, an effect which was antagonised by 10(-6) M 8-cyclopentyltheophylline (8-CPT). The depression of the MSR, caused by 4 min of hypoxia (either stop-flow or anoxic superfusion), was prevented by 10(-6) M 8-CPT. These results provide strong evidence for a critical involvement of adenosine in mediating early synaptic depression evoked by a brief period of hypoxia.
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PMID:Involvement of adenosine in synaptic depression induced by a brief period of hypoxia in isolated spinal cord of neonatal rat. 319 1

In pericruciate cortex-ablated 'pyramidal cats', discharge changes in single neurons of ventral thalamic nuclei were studied, following stimulation of ipsilateral medullary (MPT) and contralateral cervical (CPT) pyramidal tract. It was seen that cells in ventrolateral nucleus, ventroanterior nucleus and ventromedial nucleus were not significantly (2.2%) modified by impulses coming from MPT and CPT. Conversely, a very high percentage (58.8%) of cells in ventrobasal complex (VB) responded to MPT stimulation (64.4% in ventroposterolateral nucleus, VPL, and 40.7% in ventroposteromedial nucleus, VPM). A considerable number (34.8%) of VPL cells responsive to MPT, were influenced by CPT, while none of the cells in VPM were. The most frequent effect observed in VB neurons, on MPT and CPT stimulation, was excitation followed by depression of discharge.
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PMID:Pyramidal influences on ventral thalamic nuclei in the cat. 631 70

The purpose of this paper is to examine the treatment patterns and costs of treatment for depressive disorders in the private sector of the United States. Based on the 1987-1989 calendar year MEDSTAT claim data, 40,898 patients were identified with a principal diagnosis of depressive disorder. Among a list of CPT-4 code procedures, individual psychotherapy had the highest frequency of usage followed by individual visits. Compared to individual psychotherapy, group/family psychotherapy had a much lower frequency of usage. Very few diagnostic episodes had laboratory work. In inpatient settings, costs of physician procedures and laboratory services were 2 times greater for patients with major depression or bipolar disorder than for patients with depression not otherwise specified (NOS) or dysthymic disorder. As expected, costs varied widely per episode. As the severity of illness increased, the cost variation became wider.
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PMID:Depressive disorders: treatment patterns and costs of treatment in the private sector of the United States. 748 8

Participation of adenosine receptors in the depression of synaptic transmission during hypoxia, and the production of multiple populations spikes in the pyramidal neurons following hypoxia, has been investigated in the CA1 area of the rat hippocampal slice. A method is presented for analysing such hyperexcitability, using input/output curves of the second population spike. This method provides evidence that rebound hyperexcitability following hypoxia or prolonged adenosine-mediated inhibition results from an increase in excitability of the CA1 pyramidal neurons rather than from an increase in excitatory neurotransmitter release. Hypoxia-induced depression of the synaptic components of evoked field potentials was blocked in a concentration dependent manner by the selective A1 receptor antagonist 8-cyclopentyltheophylline (8-CPT), demonstrating extracellular accumulation of adenosine during hypoxia. Upon reoxygenation of slices following 30 min hypoxia, multiple population spikes were evoked by a single orthodromic stimulus in slices that exhibited only a single population spike prior to hypoxia. Such post-hypoxic hyperexcitability was not prevented by superfusion of slices with 8-CPT during hypoxia. Depression of synaptic transmission by 30 min superfusion of slices with 50 microM adenosine was also followed, upon washout, by the appearance of multiple population spikes. However, such hyperexcitability could not be produced by superfusion with adenosine analogues selective for A1 receptors, cyclopentyladenosine, selective for A2a receptors, 2-p-(2-carboxyethyl)phenetheylamino-5'-ethylcarboxamidoadenosine (CGS 21680), or active at A2a and A2b receptors, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine, suggesting that adenosine receptors other than the A1, A2a or A2b subtypes are involved in its generation.
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PMID:Hyperexcitability in CA1 of the rat hippocampal slice following hypoxia or adenosine. 760 56

We have investigated the effects of cAMP-enhancing agents on depolarization-induced membrane capacitance increases (delta Cm) in single rat pancreatic B-cells. Concentrations of IBMX, 8-CPT cAMP and forskolin, which enhance cAMP and insulin release, all enhance depolarization-induced delta Cm's seen in response to single voltage-clamp pulses and reduce the depression of delta Cm responses often seen with trains of pulses. These effects often occur in the absence of changes in peak Ca2+ current or the total Ca2+ charge entry during the depolarizing pulse. These data suggest that cAMP-modulating maneuvers may directly affect the mechanism of insulin granule mobilization into a readily releasible store or fusion at a discharge site.
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PMID:Enhancers of cytosolic cAMP augment depolarization-induced exocytosis from pancreatic B-cells: evidence for effects distal to Ca2+ entry. 769 89

The incidence of mortality from cardiovascular diseases in higher in diabetic patients. The cause of this accelerated cardiovascular disease is multifactorial and, although atherosclerotic cardiovascular disease in association with well-defined risk factors has an influence on morbidity and mortality in diabetics, myocardial cell dysfunction independent of vascular defects have also been defined. We postulate that these adverse cardiac effects could presumably result as a consequence of the following sequence of events. Major abnormalities in myocardial carbohydrate and lipid metabolism occur as a result of insulin deficiency. These changes are closely linked to the accumulation of various acylcarnitine and coenzyme derivatives. Abnormally high amounts of metabolic intermediates could cause disturbances in calcium homeostasis either directly or indirectly through structural and functional subcellular membrane alterations. Over time, chronic abnormalities such as reduced myosin ATPase activity, decreased ability of the sarcoplasmic reticulum to take up calcium as well as depression of other membrane enzymes such as Na(+)-K+ ATPase and Ca(2+)-ATPase leads to changes in calcium homeostasis and eventually to cardiac dysfunction. More importantly from the point of view of pharmacological intervention, during the initial stages, acute disturbances in both the glucose and FFA oxidative pathways may provide the initial biochemical lesion from which further events ensue. Thus therapies which target these metabolic aberrations in the heart during the early stages of diabetes, in effect, can potentially delay or impede the progression of more permanent sequelae which could ensue from otherwise uncontrolled derangements in cardiac metabolism. There is little dispute that an attempt should be made to lower raised plasma triglyceride and FFA levels. This would decrease the heart's reliance on fatty acids and, hence, overcome the fatty acid inhibition of myocardial glucose utilization. In this regard, the likely application of fatty acid oxidation inhibitors (CPT inhibitors, beta-oxidation inhibitors, sequestration of mitochondrial CoA) is also apparent.
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PMID:Myocardial substrate metabolism: implications for diabetic cardiomyopathy. 776 Mar 40

The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3-dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal and postictal events in rats subjected to maximal electroshock (MES). MES induces the ictal event of hindlimb tonic extension (HLTE) followed by postictal depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of PID without affecting HLTE, further confirming involvement of adenosine in PID. Carbamazepine and sodium valproate were studied independently and were coadministered with 8-CPT to determine if their anticonvulsant activity was modulated by adenosine and if they altered PID. 8-CPT did not antagonize the seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal events whereas SV had no significant effect. These observations further confirm a role for adenosine in postictal phenomena.
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PMID:Involvement of adenosine in postictal events in rats given electroshock. 813 42

The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein. Among the mechanisms that could contribute to the depression of neurotransmitter release is reduced entry of calcium through channels located in the presynaptic terminal. In the present study, we have examined the effects of adenosine on high-voltage-activated (HVA) calcium currents in motoneurons, the presynaptic cells of the neuromuscular junction. The motoneurons were isolated from embryonic mice, placed in primary tissue culture for 16 hr, and analyzed by means of the whole-cell patch-clamp technique. Adenosine (40 microM) reduced both transient and sustained components of HVA calcium current. This effect was blocked by the A1 antagonist 8-cyclopentyltheophylline (CPT; 100 nM) and was mimicked by the A1 agonist N6-cyclohexyladenosine (CHA; 50 nM to 10 microM) but not by the A2a agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine (CGS-21680; 1 micron). Pretreatment with pertussis toxin (200 ng/ml, > 16 hr) abolished the depression of HVA calcium current by adenosine receptor activation. Brief (3 min) exposure of the cells to 10 microM omega-conotoxin GVIA irreversibly blocked a part of the HVA current, which can therefore be attributed to N-type channels; the remaining current was unaffected by adenosine receptor activation. Hence, it appears that adenosine decreases only the N-current portion of HVA current and that this inhibition occurs via an A1 receptor linked to a pertussis toxin-sensitive G protein. Other investigators have shown that N-type channels do not play a primary role in eliciting transmitter release at the mammalian neuromuscular junction. Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels.
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PMID:Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. 820 77

The effect of incubation with the protein kinase C activator, 4 beta-phorbol 12,13-dibutyrate (beta-PDBu) on the electrophysiological responses to hypoxia and combined hypoxia and hypoglycemia was investigated in the rat hippocampal slice. Preincubation with beta-PDBu prevents adenosine-mediated inhibition of synaptic transmission under normoxic, normoglycemic conditions. beta-PDBu preincubation also reduces the adenosine-mediated hypoxia-induced depression of synaptic transmission revealing a substantial adenosine-independent hypoxia-induced depression of synaptic transmission. During combined hypoxia and hypoglycemia, slices preincubated in beta-PDBu display a significant shortening of the time of anoxic depolarization, an effect of beta-PDBu that is not mimicked by application of the adenosine antagonist cyclopentyltheophylline (8-CPT). It is concluded that the state of PKC activation may influence the electrophysiological responses to hypoxia and ischemia.
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PMID:Phorbol ester alters the electrophysiological responses to hypoxia and ischemic-like conditions in the rat hippocampal slice. 858 22


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