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)

Inotropic responses of isolated cardiac preparations from rats with glycerol-induced acute renal failure (ARF) were recorded, following a range of cardiac stimulants. Left atria of rats with ARF showed diminished inotropic responses only to the calcium agonist Bay K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5 -carboxylate) whilst right ventricular strips exhibited reduced responses to isoprenaline, 3-isobutyl-1-methylxanthine, Ca2+ and Bay K 8644. Investigations of cardiac mitochondrial respiration indicated that there is a site-unspecific 'pseudo' uncoupling of oxidative phosphorylation in ARF but that electron transport is unaffected. This uncoupling of oxidative phosphorylation did not have any detectable effect on either levels of total adenine nucleotides and creatine phosphate or cellular energy charge. Measurements were also made of the activity of pyruvate dehydrogenase which provides an index of mitochondrial Ca2+ levels. The proportion of pyruvate dehydrogenase in its active form was threefold higher following isoprenaline injection in hearts of rats with ARF compared with controls. The results suggest that in hearts of rats with ARF there is a change in the number, affinity, efficacy or coupling of the dihydropyridine receptor on the L-type calcium channel. Moreover, in the ventricle, a defect in cellular Ca2+ control, resulting in an increase in mitochondrial Ca2+ uptake, may contribute to the depression of inotropic response to the range of cardiac stimulants tested.
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PMID:Cardiac function in rats with acute renal failure. 128 76

The effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine were evaluated. Verapamil (10-80 mg/kg), diltiazem (20-120 mg/kg) and nicardipine (20-160 mg/kg), when administered subcutaneously, produced a dose-dependent reduction in forepaw tremor and weight loss during the abstinence reaction; jumping was also reduced by all three drugs, although the effect was not statistically significant in the case of nicardipine. By contrast, the calcium agonist Bay K 8644 (0.5-2 mg/kg, SC) increased forepaw tremor and weight loss, although this latter effect did not reach statistical significance. The effects of the calcium channel active drugs on the rotarod test were also explored, no correlation appearing with the results observed in abstinence (except for the jumping response), which suggests that the withdrawal results are not influenced by motor incoordination or unspecific CNS depression. These findings suggest that L-type calcium channels probably play an important role in withdrawal after acute morphine dependence. Taken together with other observations in chronic models, these results show that calcium channels are similarly involved in morphine abstinence after acute and chronic dependence, in contrast to the differences in the content and uptake of neuronal calcium induced by morphine under both conditions.
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PMID:Differential effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine. 171 13

The involvement of L-type calcium channels in heterosynaptic long-term depression (LTD) of the stratum radiatum input to area CA1 was studied in rat hippocampal slices. LTD of the radiatum field excitatory postsynaptic potential (EPSP) and population spike, produced by tetanization of the alveus in the presence of picrotoxin, was blocked by the calcium antagonist nimodipine and by a monoclonal antibody to the L-type calcium channel. LTD was produced in the absence of picrotoxin when the L-type calcium channel agonist, BAY-K8644, was applied. This effect was also blocked by nimodipine. These results indicate that L-type calcium channels are involved in heterosynaptic long-term depression.
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PMID:The involvement of L-type calcium channels in heterosynaptic long-term depression in the hippocampus. 172 Nov 10

We examined the role of dihydropyridine-sensitive Ca2+ channels in long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus of pentobarbital-anaesthetized rats. Intrahippocampal infusions (1.0 microliter) of nimodipine (20 mM) and nifedipine (20 mM), two antagonists of L-type voltage-sensitive calcium channels (VSCC), 60 min prior to medial perforant path tetanization, completely blocked the appearance of LTD in the lateral perforant path, without significantly affecting the simultaneous induction of medial path LTP. Heterosynaptic LTD was not significantly different from control animals following infusions of the L-type calcium channel agonist BAY-K8644 (1 mM). These results suggest that L-type VSCC activity is necessary for the induction of heterosynaptic LTD in the dentate gyrus in vivo.
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PMID:L-type voltage-sensitive calcium channel antagonists block heterosynaptic long-term depression in the dentate gyrus of anaesthetized rats. 751 41

We and others have proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to determine if cytokine-stimulated NO production could also regulate beating rates of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 hours (p < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(-5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(-3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n = 12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect of the cytokines on the spontaneous beating rates of the cardiac cells (p < or = .01; n = 12 for each). These results strongly suggest that cytokines and NMA affect cardiac myocyte spontaneous beating rates through mechanisms independent of NO.
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PMID:Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L-NMMA, on cardiac myocytes. 752 6

Homosynaptic long-term depression (LTD) was studied in hippocampal slices from 12-18-d-old rats using field EPSP recording in the apical dendritic layer of CA1 pyramidal cells. Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartic acid (NMDA) receptor-mediated components of the field EPSP were obtained in parallel using early and late measurements of a dual-component EPSP in a low-magnesium solution. LTD was induced by low-frequency stimulation (LFS; 2 Hz for 10 min), resulting in equal relative changes of the AMPA and NMDA receptor-mediated components. Under conditions when the AMPA receptor-mediated component was fully blocked, a similarly sized LTD was observed for the pure NMDA receptor-mediated EPSP (measured as initial slope or peak amplitude). Equal changes in AMPA and NMDA receptor-mediated components occurred also upon application of the adenosine agonist N6-cyclohexyladenosine (CHA), known to act by decreasing transmitter release. On the other hand, LTD was found to interact in a multiplicative manner with the presynaptic release changes induced by CHA and by paired-pulse facilitation. The induction of the LTDs of both AMPA and NMDA receptor-mediated EPSPs was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid and by the phosphatase inhibitor okadaic acid. Partial blockade of LTD by okadaic acid resulted in equal partial blockade of the LTDs of the AMPA and NMDA receptor-mediated components. On the other hand, the L-type calcium channel blocker nifedipine, the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, the nitric oxide synthase inhibitor N omega-nitro-L-arginine, and the heme oxygenase inhibitor protoporphyrin IX zinc(II) had no effect on LTD of either the AMPA or the NMDA receptor-mediated component. These results of equal changes of AMPA and NMDA receptor-mediated components of the field EPSP in association with LTD, and the consistent parallelism of effects or noneffects on these components by various receptor antagonists and enzyme inhibitors, seem more easily explained by a presynaptic locus for LTD than by a postsynaptic one.
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PMID:On the linkage between AMPA and NMDA receptor-mediated EPSPs in homosynaptic long-term depression in the hippocampal CA1 region of young rats. 754 Jun 77

Modulation of L-type calcium channels by the five cloned muscarinic receptors was studied by expression of the receptors in NIH 3T3 cells. Application of acetylcholine (ACh) to cells transfected with m1-m5 resulted in a reduction in the L-type calcium current amplitude. Elevations in intracellular cAMP concentrations induced by 8-bromo-cAMP or forskolin resulted in no discernible change in the L-type calcium current. In addition, treatment with Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS), a protein kinase A (PKA) inhibitor, had no effect on the L-type currents. Conversely, application of phorbol dibutyrate, an activator of protein kinase C (PKC) or 8-bromo-cGMP, an activator of cGMP-dependent protein kinase (PKG), reduced the calcium currents. Incubation of the cells with KT5823, an inhibitor of PKG, resulted in a reduction of the response to 8-bromo-cGMP. The ACh-induced depression of L-type calcium current amplitude was sensitive to pertussis toxin (PTX) in cells transfected with the m2 or m4 receptor subtype. The m2-muscarinic-receptor-induced inhibition of the L-type calcium current was attenuated by preincubation of the cells with 8-bromo-cAMP and was unaffected by KT5823 or by calphostin C. The m1-muscarinic-receptor-induced inhibition of the L-type calcium conductance was insensitive to PTX treatment. However, the m1-induced response was blocked by preincubation of the cells with calphostin C. The present data indicate that the m2 (and possibly also the m4) muscarinic receptors inhibit the L-type calcium conductance by a reduction in cAMP concentration and that the m1 (and possibly also the m3 and m5) muscarinic receptors inhibit the L-type calcium channel via activation of PKC.
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PMID:Inhibition of the L-type calcium channel by the five muscarinic receptors (m1-m5) expressed in NIH 3T3 cells. 900 Apr 30

Homosynaptic long-term depression (LTD) of synaptic efficacy was induced in field excitatory postsynaptic potentials by administration of 900 pulses at either 1 or 3 Hz in 2- to 3-wk-old Sprague-Dawley rats. The stimulation was administered via a bipolar stimulating electrode placed immediately adjacent to the recording electrode in the stratum radiatum region of the hippocampal CA1 subfield. Equivalent LTD induction occurred whether the slices were maintained at room temperature or at 32 degrees C. Lowering bath Ca2+ to 0 mM, or increasing it to 4 mM, prevented the induction of the depression. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (50 microM) reversibly blocked the induction of homosynaptic LTD. In addition, the L-type voltage-gated calcium channel (VGCC) antagonist nimodipine (10 microM) and the R- and T-type VGCC antagonist NiCl2 (25 microM) also prevented homosynaptic LTD induction. These results indicate that in addition to N-methyl-D-aspartate receptor activity, Ca2+ influx via VGCCs can play an important role in the induction and expression of LTD induced by low-frequency stimulation in the hippocampal formation.
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PMID:Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro. 908 30

The effects of the glucocorticoid receptor agonist RU-28362 on homosynaptic long-term depression (LTD) were examined in hippocampal slices obtained from adrenal-intact adult male rats. Field excitatory postsynaptic potentials were evoked by stimulation of the Schaffer collateral/commissural pathway and recorded in stratum radiatum of area CA1. Low-frequency stimulation (LFS) was delivered at LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity). LFS of the Schaffer collaterals did not produce significant homosynaptic LTD in control slices. However, identical conditioning in the presence of the glucocorticoid receptor agonist RU-28362 (10 microM) produced a robust LTD, which was blocked by the selective glucocorticoid antagonist RU-38486. The LTD induced by glucocorticoid receptor activation was dependent on N-methyl-D-aspartate (NMDA) receptor activity, because the specific NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the facilitation of LTD was not due to a potentiation of the isolated NMDA receptor potential by RU-28362. The facilitation of LTD by RU-28362 was also blocked by coincubation of the L-type voltage-dependent calcium channel (VDCC) antagonist nimodipine. Selective activation of the L-type VDCCs by the agonist Bay K 8644 also facilitated LTD induction. Both nimodipine and D-AP5 were effective in blocking the facilitation of LTD by Bay K 8644. These results indicate that L-type VDCCs can contribute to NMDA-receptor-dependent LTD induction.
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PMID:Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels. 924 54

Of 30 patients with treatment-refractory affective illness, 10 showed a moderate to marked response to blind nimodipine monotherapy compared with placebo on the Clinical Global Impressions Scale. Fourteen inadequately responsive patients (3 unipolar [UP], 11 bipolar [BP]) were treated with the blind addition of carbamazepine. Carbamazepine augmentation of nimodipine converted four (29%) of the partial responders to more robust responders. Patients who showed an excellent response to the nimodipine-carbamazepine combination included individual patients with patterns of rapid cycling, ultradian cycling, UP recurrent brief depression, and one with BP type II depression. When verapamil was blindly substituted for nimodipine, two BP patients failed to maintain improvement but responded again to nimodipine and remained well with a blind transition to another dihydropyridine L-type calcium channel blocker (CCB), isradipine. Mechanistic implications of the response to the dihydropyridine L-type CCB nimodipine alone and in combination with carbamazepine are discussed.
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PMID:Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness. 2221 56


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