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)

Insulin release in response to glucose was measured after culture of islets from ob/obmice in a medium deficient in Ca2+. When present at a concentration of 6 mmol/l, glucose inhibited, insulin release. After activation of the alpha2-adrenergic receptors by 1 mumol/l clonidine also 20 mmol/l glucose became inhibitory. The inhibitory action of glucose on insulin release disappeared in the presence of 1 mmol/l dibutyryl cyclic AMP. Raising the glucose concentration from 3 to 20 mmol/l resulted in increased cytoplasmic Ca2+ after an initial depression. Whereas clonidine removed the Ca2+ increase, this phase was partly restored after simultaneous addition of dibutyryl cyclic AMP. It is concluded that cyclic AMP plays a major role in controlling the balance between the stimulatory and inhibitory components in the glucose action on insulin release.
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PMID:Reversal of glucose-induced inhibition of insulin release by dibutyryl cyclic AMP. 255 Feb 72

1. Experiments have been performed with the dual intent of analysing the mechanism by which AH 21-132 relaxes airways smooth muscle and determining whether the effects of this compound can be distinguished from those of theophylline. 2. AH 21-132 (0.25-8 microM) and theophylline (1-1000 microM) each caused concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachealis. The maximal effect of AH 21-132 was equivalent to that of theophylline. No evidence was obtained that the tissue became sensitized or desensitized to the action of AH 21-132. 3. Propranolol (1 microM) profoundly antagonized the tracheal relaxant action of isoprenaline but not that of AH 21-132. 4. In indomethacin (2.8 microM)-treated tissues, tone was induced by K+-rich (120 mM) Krebs solution, acetylcholine (ACh, 1 mM) or histamine (200 microM). Log concentration-relaxation curves for AH 21-132, isoprenaline and theophylline were all moved to the right in the presence of the spasmogens, the smallest rightward shift being induced by histamine and the greatest by ACh. While maximal effects of AH 21-132 and theophylline were unaffected by the spasmogens, that of isoprenaline was reduced by KCl and ACh. 5. In tissues treated with indomethacin (2.8 microM), AH 21-132 (0.1-100 microM) inhibited the spasmogenic effects of potassium chloride (KCl), ACh and histamine in a concentration-dependent manner. The inhibition was characterized by rightward shifts in the spasmogen concentration-effect curves with depression of their maxima. 6. In tissues treated with both indomethacin (2.8 microM) and ACh (1 mM), the removal of tracheal epithelium caused a small but significant leftward shift in the log concentration-relaxation curve for AH 21-132 but did not alter that for theophylline. 7. In tissues treated with indomethacin (2.8 microM) and maintained at 12 degrees C, theophylline (0.1-3.2 mM) caused concentration-dependent spasm. This effect was not shared by AH 21-132. 8. AH 21-132 (0.1-1000 microM) more potently inhibited the activity of cyclic AMP-dependent than of cyclic GMP-dependent phosphodiesterase derived from homogenates of guinea-pig trachealis. Theophylline, too, inhibited these enzymes but was less potent in each case than AH 21-132 and did not exhibit selectivity for the cyclic AMP-dependent enzyme. 9. It is concluded that AH 21-132 exerts a non-specific (i.e. effective no matter what agent is used to support tone) relaxant effect on the trachealis muscle which does not involve the activation of beta l-adrenoceptors. The profile of the relaxant action of AH 21-132 more closely resembles that of theophylline than that of isoprenaline. However, AH 21-132 can be differentiated from theophylline in that: (a) its relaxant potency is increased by epithelial removal; (b) it does not cause tracheal spasm; (c) it exhibits selectivity as an inhibitor of cyclic AMP-dependent as opposed to cyclic GMP-dependent phosphodiesterase. It is possible that the relaxant effects of AH 21-132 are related to its ability to inhibit cyclic nucleotide phosphodiesterases.
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PMID:Analysis of the relaxant effects of AH 21-132 in guinea-pig isolated trachealis. 255 42

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle. The effective concentration ranges were 0.1-1OOO microM and 1-1000 microM, respectively. Theophylline, too, inhibited these enzymes but in each case was less potent than AH 21-132. 8. It is concluded that AH 21-132 is devoid of antagonist activity at adenosine Al receptors which modulate ACh release from intramural cholinergic nerves in the ileum. At concentrations greater than IO microM, AH 21-132 has a relaxant effect on intestinal smooth muscle characterized by suppression of spontaneous action potentials but by minor change in resting membrane potential. AH 21-132 previously has been reported to depress the spontaneous tone of trachealis muscle with an EC50 value of less than lO microM and the present experiments therefore show that this agent is much less potent in inhibiting intestinal muscle. This potency difference cannot be attributed to a tissuerelated difference in the potency of AH 21-132 as an inhibitor of cyclic AMP- or cyclic GMPdependent phosphodiesterases.
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PMID:Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci. 255 43

Adenylate cyclase (AC) activity in skeletal muscle cells isolated from new born rats was increased with time in culture, indicating the presence of heterologous supersensitivity as in the case of denervation in vivo. The effect of addition of calcitonin gene-related peptide (CGRP) to the cultures of skeletal muscle cells on increase in the AC activity was studied. The increases in AC activity stimulated by CGRP, isoproterenol, NaF and forskolin were depressed by exposure to CGRP (1 microM) for 24 hours, depression of CGRP-stimulated AC activity being the greatest. The extent of reduction in increase in AC activity depended on the concentration of CGRP and duration of exposure. The AC activity stimulated by CGRP was also decreased by exposure to dbc-AMP for 24 hours. When muscle cells were exposed to CGRP for 3 days, no significant difference among the AC activity stimulated by NaF, forskolin and CGRP was seen. These results suggest that exposure to CGRP for one day caused mainly homologous desensitization of the CGRP receptor, whereas exposure for 3-4 days caused heterologous desensitization of the AC catalytic unit, perhaps by elevating the c-AMP level in the cells. These results imply that CGRP, which is located in the motor nerve terminal, may play a role as a physiological trophic factor on skeletal muscle.
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PMID:Effects of calcitonin gene-related peptide on the adenylate cyclase system in cultured rat skeletal muscle cells. 260 71

The present paper gives a review of German studies concerning the AMP and AMDP system that have been published since 1983. The test manual to the AMDP-system, published 1983, is complemented herewith. The following topics are discussed: Syndromes/scales on the basis of psychological and somatic outcomes, studies on reliability (especially interrater reliability); capability to differentiate diagnoses; comparison with other assessment instruments, especially biological parameters; results of several diagnoses (schizophrenia, affective disorders, depression etc.); range of application (psychopharmacological studies, diagnostic questions, etc.). The review points out that the AMDP system covers a very wide and elaborate range. Some topics are pointed out that would merit additional study.
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PMID:[Evaluation of the system of the Study Group of Methodology and Documentation in Psychiatry based on recent literature (1983 to 1987)--a review]. 267 9

The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.
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PMID:Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy. 271 73

The present study was initiated to test to what extent preovulatory follicles are dependent on oxygen supply for maintaining their response to luteinizing hormone (LH). Female rats of the Sprague-Dawley strain were injected with 6 IU of pregnant mare serum gonadotropin (PMSG) on their 26th day of life. For in vitro experiments rats were killed 48-52 h after PMSG injection. Preovulatory follicles were dissected free, pre-incubated for 30 min and then incubated for 3 h without or with luteinizing hormone (LH, 1 microgram ml-1 medium) under different oxygen tensions in the gas phase (100, 13, 6 and 0 kPa). After incubation the accumulation of progesterone, cyclic-3',5'-adenosine monophosphate (cyclic AMP) and lactic acid were measured in the incubation media. Follicular adenosine-5'-triphosphate (ATP) content was measured in vivo (48-60 h after PMSG injection) immediately after isolation as well as after the incubation. Follicles isolated in vivo, during and after the ovulatory endogenous gonadotropin surge showed a depression in follicular ATP levels compared with levels before, suggesting that gonadotropins stimulate the follicle on the expense of ATP levels during the course of the preovulatory day. During a step-wise decrease of oxygen tension in vitro the preovulatory follicle maintained its response to LH as measured by progesterone and cyclic AMP accumulation. The preovulatory follicle could apparently compensate by increasing glycolysis, as measured by an increase in lactic acid accumulation. Tissue ATP levels were during these conditions maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen dependency of preovulatory follicles from pregnant mare serum gonadotropin-treated immature rats. 282 Jan 96

Beta-adrenoceptor-mediated cyclic AMP formation was found to be increased in leukocytes from manic-depressive patients during untreated depression when compared with euthymic patients treated with antidepressants. The difference was dependent on the stimulation used (isoprenaline or a combination of noradrenaline and phentolamine) and was only significant when the combination was used. Histamine-stimulated cyclic AMP formation in leukocytes was enhanced in patients with untreated depression, both when compared with euthymic patients suffering from manic-depressive illness, with or without treatment with antidepressant drugs, and also when compared with control persons without any known psychiatric disease. Although at variance with the results of some other studies on the same topic, the results of the present study indicate that changes in receptor function in leukocytes may be a state-dependent marker in depressive illness.
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PMID:Enhanced histamine- and beta-adrenoceptor-mediated cyclic AMP formation in leukocytes from patients with endogenous depression. 282 89

This paper reviews briefly the very common finding in chronic antidepressant use, of subsensitivity of the beta-adrenoreceptor-linked cyclic AMP system. This subsensitivity is observed with a number of different antidepressant treatments, including pharmacological, electrical and sleep deprivation. The subsensitivity requires intact noradrenergic and serotonergic systems, functionally linking the two neurotransmitters most often implicated in depression. Thyroid hormones and estrogens also cause subsensitivity, while the opposite effect is seen with Reserpine and Propranolol. A modified conditioning/sensitization model is proposed, implicating psychosocial stressors with a biological inability to down-regulate beta-adrenoreceptors.
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PMID:The antidepressant effect of beta-adrenoreceptor subsensitivity: a brief review and clinical implications. 283 4

The effects of cyclic nucleotide analogs and related agents on the Ca2+ dependent action potentials of cultured rat aortic smooth muscle cells (reaggregates) were examined. The action potentials were elicited by electrical stimulation in the presence of tetraethylammonium (TEA, 5-15 mM). Superfusion of the aortic cells with analogs of cyclic AMP (dibutyryl or 8-bromo-cyclic AMP, 1 mM), isoproterenol (1-10 microM) and forskolin (1-10 microM) depressed and abolished the TEA-induced action potentials. Abolition of the action potentials by these agents was reversible and was accompanied by some hyperpolarization of the membrane. Superfusion with 8-bromo-cyclic GMP (0.1-1 mM) also depressed or abolished the TEA-induced action potentials, whereas dibutyryl cyclic GMP (1 mM) and sodium nitroprusside (10 microM) had little effect. Synthetic atrial natriuretic factor (0.01-0.1 microM) had inhibitory effects in most experiments. Thus, depression of membrane excitability may be a contributing factor in the relaxation of aortic smooth muscle produced by some agents that increase intracellular levels of cyclic nucleotides.
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PMID:Cyclic nucleotides depress action potentials in cultured aortic smooth muscle cells. 283 Jan 20


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