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 Excitatory junction potentials (e.j.ps) were recorded with intracellular microelectrodes from smooth muscle cells of the mouse isolated vas deferens. The amplitude of the e.j.p. was used as a measure of transmitter release evoked by applying single pulse stimuli to the intramural nerves. 2 Cyclic adenosine 3',5'-monophosphate (cyclic AMP) and dibutyryl cyclic AMP (db cyclic AMP, up to 1 mM) depressed the amplitude of e.j.ps, probably by interacting with extracellular sites on the nerve terminals, similar to those responsive to adenosine. 3 The phosphodiesterase inhibitors, 1-methyl-3-isobutyl xanthine (IBMX) and 1-ethyl-4-hydrazino-1H-pyrazolo(3,4-b)pyridine-5-carboxylic acid, ethylester, hydrochloride (SQ20,006) increased e.j.p. amplitude; this increase was much greater when the phosphodiesterase inhibitor was applied together with db cyclic AMP. 4 Neither the cyclic nucleotides nor the phosphodiesterase inhibitors altered the resting membrane potential of smooth muscle cells. 5 The amplitude of the e.j.p. was depressed by normorphine, D-Ala2-Met5-enkephalinamide (DAEA) and D-Ala2-D-Leu5-enkephalin (DADL) with respective EC50s of 560 nM, 49 nM and 510 pM. 6 There was no change in the EC50 for normorphine in the presence of cyclic AMP (1 mM) or in the presence of a combination of IBMX (50 microM) and db cyclic AMP (500 microM). Similarly, the depression of the e.j.p. by DAEA or DADL was not affected by the combination IBMX (500 microM) and db cyclic AMP (250 microM). 7 These findings provide evidence against the hypothesis that a reduction in cyclic AMP levels in nerve terminals is an essential step in the inhibition by opiates and opioid peptides of transmitter release.
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PMID:A study of the role of cyclic adenosine 3',5'-monophosphate in the depression by opiates and opioid peptides of excitatory junction potentials in the mouse vas deferens. 625 91

1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (-)-isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa. 2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol. 3. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated. 4. The results support the involvement of cyclic AMP in the depressant effect of beta-adrenoreceptor agonists on slow-contracting mammalian skeletal muscle.
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PMID:Effects of isoprenaline, levodopa and a phosphodiesterase inhibitor (ICI 63,197) on cyclic AMP levels and contractions of soleus muscles in anesthetized cats. 625 31

Continuously regenerating stratified squamous epithelia form an interesting model for examining mechanisms controlling the balance between rates of cell formation and cell maturation and death. In vitro assays of rates of glycolysis and amino acid incorporation of epidermal sheets free from dermal contamination were used to examine rates of metabolism in both normal and hyperplastic epidermis after treatment with various adrenergic agonists and cAMP. Epinephrine and isoproterenol over the concentration range of 1 x 10(-9) to 1 x 10(-5) M depressed the rates of glycolysis and amino acid incorporation in normal epidermis. Dibutyryl cyclic AMP produced a 73 to 78% depression in metabolic activity and its action was enhanced by the addition of theophylline. The alpha adrenergic agonist norepinephrine produced similar reductions. When epidermal samples were treated with hexadecane to induce a mild hyperplasia, depressant effects of isoproterenol and epinephrine were lost, but dibutyryl cyclic AMP and norepinephrine still reduced metabolic activity. The results suggest that adrenergic agents and their putative second messenger cAMP cause reductions in epidermal metabolic activity, an effect similar to their effects on cell proliferation, and that increased rates of proliferation are associated with loss of beta adrenergic responsiveness of the epidermis.
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PMID:The effects of alpha and beta adrenergic agonists and cyclic adenosine 3':5'-monophosphate on epidermal metabolism. 626 12

The author studied the effect of the elevated cAMP content on the efficacy of the synaptic systems of the hippocamp. The population spike (PS) response to Shaffer collateral electric stimulation was recorded in the CA1 field. The PS amplitude served as criterion of cell reactivity. Use was made of dibutyryl-cAMP (db-cAMP), an analog of cAMP, well penetrating the membrane, and of 8-/Cl-acetylaminoethylthio/-cAMP, an inhibitor of phosphodiesterase (PDE) of irreversible action, leading to cAMP accumulation by the cell. Introduction of db-cAMP into the bath medium evoked an abrupt increase in the PS amplitude, followed by gradual diminution of the response until complete depression PDE inhibitor evoked a gradual and irreversible increase of the PS amplitude. The data suggest that the secondary messenger cAMP plays an important role in synaptic processes occurring in the hippocamp.
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PMID:[Role of cAMP in regulating hippocampal neuronal reactivity in vitro]. 628 36

In the nervous system of the leech Hirudo medicinalis it has been possible to study short-term plastic changes. Depression and facilitation have been demonstrated in the fast conducting system (FCS) activity; this pathway consists of a chain of electrically linked neurons present in each ganglion. In semi-intact animals or in preparation of nerve cord and segments of body wall, both electrical stimulation of peripheral roots and tactile stimulation of the skin induced, after repetitive stimulation (0.1/s) a prolonged decrement of FCS response. Strong nociceptive stimulation applied onto the head or the body wall produced a sustained facilitation of the waned response. The same potentiation has been observed by perfusing the isolated ganglion with serotonin (5 x 10(-5) M). Such a potentiation is abolished by preincubation with methysergide, an antagonist of serotonin, and with imidazole, a cAMP-phosphodiesterase activator. Such an effect is mimicked by an analog of cAMP, db-cAMP. Simultaneous recordings of both T neurons (intracellularly) and FCS firing discharge showed that, during FCS response decrement, the T cell activity remained unchanged and no modification of conductance occurred, excluding therefore a detectable involvement of sensory neurons in the depression. These results suggest that short-term plastic changes of the FCS of the leech are due to a prolonged potentiation of synaptic transmission as a result of serotonin-mediated increase in cAMP.
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PMID:Role of serotonin and cyclic AMP on facilitation of the fast conducting system activity in the leech Hirudo medicinalis. 628 76

Electrical responses induced by perivasascular nerve stimulation were recorded intracellularly from the smooth muscle of dog middle cerebral artery. With nerve stimulation, the muscle membrane produced excitatory junction potential and then a slow hyperpolarization. The excitatory junction potential showed facilitation and the slow hyperpolarization showed depression phenomena, when the nerves were stimulated with twin pulses. Generation of the slow hyperpolarization was associated with an increase in the potassium conductance of the membrane and was suppressed by tetraethylammonium, which depolarized the membrane, reduced the membrane conductance, and increased the amplitude of the excitatory junction potential. Treatment with 6-hydroxydopamine abolished the excitatory junction potential, but not the slow hyperpolarization; the latter was suppressed by tetrodotoxin. The amplitude of slow hyperpolarization was decreased by application of tetraethylammonium or ATP, but was not affected by application of atropine, neostigmine, theophylline, apamin, ouabain, norepinephrine, propranolol, or guanethidine. ATP produced transient depolarization of the membrane with associated decrease in the membrane resistance. The excitatory junction potential was attributed to activation of the noradrenergic nerves, whereas the slow hyperpolarization was not generated by activation of adrenergic, cholinergic, or purinergic receptors. Inasmuch as the electrogenic Na-K pump, cAMP, and ATP were not involved in the generation of slow hyperpolarization, the possibility of an unidentified chemical transmitter should be given attention.
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PMID:Neurogenic electrical responses of single smooth muscle cells of the dog middle cerebral artery. 629

Sensitization of the gill withdrawal reflex results from presynaptic facilitation at the excitatory synapses made by sensory neurons on gill motor neurons. Facilitation is accompanied by an increase in the duration of the action potential in sensory cells because of the depression of a K+ current. This results in an increasd influx of CA2+ and a greater release of transmitter from sensory neurons. There is evidence that serotonin is the facilitating transmitter and that the depression of the K+ current by serotonin mediated by cAMP-dependent protein phosphorylation. To test further the role of the cAMP-dependent protein kinase and of protein phosphorylation in sensitization, we have attempted to prevent or reverse the development of the electrophysiological correlates that accompany sensitization. We have pressure-injected sensory neurons with a specific and a stable protein inhibitor of the cAMP-dependent protein kinase both before and after the application of serotonin or the activation of the facilitator neurons. The increase in spike broadening that accompanies facilitation was prevented or diminished by injection of the inhibitor. Moreover, injection of the inhibitor could reverse fully the developed spike broadening produced by prior application of serotonin. These observations strenthen the evidence for the involvement of protein phosphorylation in presynaptic facilitation. Phosphorylation of the substrate protein evidently is quite labile and does not persist after the kinase is inhibited. Thus, the time course of short term sensitization appears to be determined by an active kinase. We think that it is likely that the mechanism for maintaining the kinase in an active form resides in the slow decay of the cAMP produced by the action of serotonin or the facilitator neurons on the sensory cells.
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PMID:Inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia. 629 79

The initial cellular reaction against the deleterious effects of shock-inducing stimuli apparently elevates the energy-producing capacity so that the cell is able to sustain its normal function. Several endocrine events are fundamentally important as triggering factors for this kind of reaction. As the shock state advances, cellular metabolism deteriorates progressively and cellular energy is exhausted. Depression of intracellular cAMP may induce cellular metabolic unresponsiveness to hormonal stimuli. Consistent degradation of high-energy substances, extreme deviation of the redox state in the NAD+-NADH system, and decrease of endogenous key substances such as L-carnitine ultimately may lead to a standstill of cellular enzymatic reactions (Fig. 13). Methods intended to sustain cellular membrane and enzymatic systems may offer the best contribution to the improvement of shock therapy.
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PMID:Metabolic deterioration in shock state and its modulation. 630 80

Cyclic AMP and cyclic GMP are important regulatory agents of lymphocyte functions. Depressed T-lymphocyte functions are frequently associated with Hodgkin's disease and suppressor monocytes have been implicated in the pathogenesis of this defect. In the present study cAMP and cGMP resting levels were measured in lymphocytes from 18 untreated patients with Hodgkin's disease using a sensitive radioimmunoassay. A significant decrease of cAMP (P less than 0.001) and, to a lesser degree, of cGMP (P less than 0.01) was found in monocyte-depleted lymphocyte suspensions from the patients compared to controls. Studies of patient and control lymphocyte subpopulations showed in patients a clear deficit of cAMP in T-depleted lymphocytes, rather than in T cells, with a low cAMP/cGMP molar ratio in both subpopulations. From this data it is clear that factors other than prostaglandin-mediated suppression of monocyte origin are involved in the pathogenesis of the T-lymphocyte depression associated with Hodgkin's disease.
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PMID:Alterations of peripheral blood lymphocyte cyclic AMP and cyclic GMP in untreated patients with hodgkin's disease. 630 67

In an attempt to further elucidate the mechanisms of fasting-depressed maximum thermogenesis and cold tolerance, norepinephrine (NE)-stimulated non-shivering thermogenesis (NST) in cold-acclimated rats was used as a functional index of possible alterations in adrenergic efficacy after fasting. Fasting decreased the magnitude of maximum NE-Stimulated NST by 18.2% [6.87 +/- 0.47 Kcal (Kg X 75 X min)-1 well-fed vs. 5.81 +/- 0.39 Kcal (Kg X 75 X min)-1 fasted], but the apparent adrenergic binding affinity was not affected [Ke = 0.43 micrograms NE min-1 well-fed vs. 0.55 micrograms NE min-1 fasted]. Pretreatment with aminophylline [15 mg Kg-1, i.p.], a phosphodiesterase inhibitor, restored the fasting-depressed NE-stimulated NST to the fed level. The results suggest that the depression of maximum thermogenesis after fasting is not due to changes in adrenergic binding characteristics but to alteration in cAMP production/degradation, resulting in decreased substrate mobilization for thermogenesis.
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PMID:Effects of fasting and aminophylline on norepinephrine-stimulated non-shivering thermogenesis. 632 99


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