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 The report of the depression by indomethacin of vasoconstrictor responses to noradrenaline and their partial restoration by prostaglandin E(2) (PGE(2)) and PGE(1) in rat isolated perfused mesenteric blood vessels was investigated. The further suggestion that prostaglandins may be necessary for the combination of noradrenaline with the alpha-adrenoceptor in this tissue was also studied.2 The reported depression by indomethacin was confirmed and was further shown to be in the form of a concentration-dependent flattening of the noradrenaline concentration-effect curve.3 A concentration-dependent restorative effect was observed for all prostaglandins studied. The decreasing order of potency for the restoration towards normal of the indomethacin-depressed responses to noradrenaline was: PGE(2), PGE(1), PGA(1), PGF(2alpha), PGA(2).4 The prostaglandins studied were not uniform in their restorative actions and could be separated into two groups. PGE(2) and PGE(1) restored responses towards the control level whereas PGA(1), PGA(2) and PGF(2alpha) increased responses to an above control level and did so over a smaller concentration range. The possibility of several prostaglandin receptors is discussed.5 At concentrations equi-effective in restoring depressed responses to control levels PGA(1) but not PGE(2), caused a parallel shift of the noradrenaline concentration-effect curve to the left and a small, gradual rise in the basal perfusion pressure.6 The reason for the differing effects remains obscure but does not seem to involve a change in the alpha-adrenoceptor as indicated by the pA(2) of phentolamine. Furthermore, the restorative and potentiating effect of PGA(1) is not mediated by blockade of neuronal uptake of noradrenaline.7 It appears that prostaglandins are required for the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels and that this effect is distal to the drug-receptor interaction. The possible involvement of prostaglandins with intracellular calcium ions is discussed.
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PMID:The influence of prostaglandins on noradrenaline-induced vasoconstriction isolated perfused mesenteric blood vessels of the rat. 20 65

Variations in the spontaneous contractile activity during 6 hours following isolation of uterine horns from proestrus, metestrus and spayed rats, were explored. In estrus and metestrus preparations the contractions declined during 60 min and between 180--200 min a progressive spontaneous recovery (abolished by indomethacin) was observed up to 360 min. Uteri from proestrus and spayed animals exhibited a continuous depression without recovery during the whole experimental period. At 60 min, uterine horns from estrus animals (which showed a marked contractile decrement) released to the suspending medium significantly less prostaglandin E-like material than at 360 min, i.e. when contractions had almost completely recovered. No modification in the amount of prostaglandin F-like material was detected accompanying these spontaneous contractile variations. In the spayed group at 60 min of functioning (i.e. when the contractile impairment was significantly smaller than at a later time) the release of PGE was greater than at 360 min. These findings suggest a possible control of rat uterine contractions by PGE, rather than by PGF.
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PMID:Is the spontaneous motility of isolated rat uterus controlled by prostaglandin E? 57 14

7-oxa-13-prostynoic acid (OPA) and polyphloretin phosphate (PPP) are believed to act as specific antagonists of prostaglandin action. In order to estimate their specificity, the inhibitory effects of these drugs were tested on the activity of adenylate cyclase from several tissues which were stimulated by prostaglandins and several other compounds. In adenylate cyclase preparation from L-fibroblasts both OPA (0.15-1.5 MM) and PPP (0.01-1.0 MG/ML) antagonized not only the stimulatory effects of PGE but also the stimulatory effects of sodium fluoride and increased enzyme activity due to the previous treatment of cell cultures by cholera toxin. Both OPA and PPP produced a dose dependent depression of adenylate cyclase activity to zero values both under basal conditions and after stimulation by sodium fluoride and various hormones in all preparations studied, including rat liver, heart, brain, epididymal adipose tissue, small intestine, renal cortex and renal medulla. The present results indicate that both prostaglandin antagonists may, in higher concentrations, act as nonspecific inhibitors of the catalytic unit of adenylate cyclase rather than specific antagonists of the prostaglandin effects on adenylate cyclase.
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PMID:7-oxa-13-prostynoic acid and polyphloretin phosphate as non-specific antagonists of the stimulatory effects of different agents on adenylate cyclase from various tissues. 123 93

There is some evidence that prostaglandin (PGE)-secreting cells may have a role in immunosuppression in cancer patients. In this work we investigated the effects of indomethacin--a PGE synthesis inhibitor, on PHA-induced lymphoproliferative response in vitro. Twenty patients with lung cancer before therapy were included in this study. When compared to controls, the patients had significant decrease of T cell number and proliferative response to PHA (p less than 0.001) and increased number of mononuclear phagocyting cells (p less than 0.001). The degree of depression of lymphocyte response did not correlate with the number of mononuclear phagocytes. The presence of indomethacin in the culture induced significant (p less than 0.01) improvement of the reactivity in high percentage (75%) of patients with diminished lymphoproliferative response to PHA. In the patients with normal lymphocyte response, indomethacin did not change reactivity to PHA. These results indicate that PGE-secreting cells may contribute to the immune depression in lung cancer patients, and that indomethacin may have therapeutical potential in some patients.
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PMID:In vitro effect of indomethacin on mitogen-induced lymphoproliferative response in lung cancer patients. 132 20

Angiotensin II inhibits nonadrenergic (purinergic) neurotransmission in the vas deferens and potentiates adrenergic neurotransmission and prostaglandin (PG)E synthesis. Other angiotensin responses are sensitive to either dithiothreitol or pertussis toxin. The present study tested the hypothesis that dithiothreitol or pertussis toxin selectively depress angiotensin responses in the vas deferens. The dithiothreitol (10 mM) eliminated the potentiation of both adrenergic neurotransmission and PGE synthesis but did not alter the depression of purinergic neurotransmission. In contrast, pertussis toxin (100 ng/ml for 3 hr) eliminated the depression of purinergic neurotransmission but had no effect on adrenergic neurotransmission or PGE synthetic responses to angiotensin II. The results are consistent with the existence of at least two transduction pathways for angiotensin II, one enhancing adrenergic neurotransmission and PGE synthesis and the other depressing purinergic neurotransmission. The results indicate that the vas deferens is a useful preparation in defining selective actions of angiotensin receptor agonists or antagonists.
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PMID:Pharmacological differentiation of angiotensin effects in the rabbit isolated vas deferens with dithiothreitol and pertussis toxin. 215 55

It was demonstrated that thymoma cells of MOLT-4 strain which are the standard cell targets of cytotoxic tests (CT) with NK-cells are rapidly releasing PGE in contact with NK-cells; as a consequence the depression of cytotoxic activity (CTA) of NK-cells takes place. The significant decrease of CTA of NK-cells was observed when the absolute number of MOLT-4 target cells participating in CT increased. Correspondingly the susceptibility of MOLT-4 cells as a target in CT is decreased. The levels of susceptibility of MOLT-4 cells to NK-cell cytotoxicity and CTA of NK-cells retained, or even increased, after the pretreatment of MOLT-4 cells with indomethacin.
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PMID:[Secretion of prostaglandin E by cells of human thymoma MOLT-4 and their sensitivity to cytotoxic action of NK-cells]. 229 74

The blood levels of stress mediators--catecholamines (adrenaline and noradrenaline), parameters characterizing the intensity of lipid peroxidation (hydroperoxides, blood antioxidant activity (from the levels of SH groups), and the content of prostaglandins F2 alpha and E (PGF2 alpha and PGE) were measured in patients with bronchial asthma and chronic asthmatic bronchitis before and after exercise. The studies have revealed that bronchial hyperreactivity to exercise is in accord with the high blood levels of catecholamines, hydroperoxides, PGF2 alpha and low content of thiol group reflecting the depression of the total antioxidant system in asthmatics. Increase of catecholamine, hydroperoxide, and PGF2 alpha levels and decrease of the total thiol group content after muscular exercise in the patients with bronchial asthma is in accord with the bronchial reactivity. Changes in the bronchoconstrictor PGF2 alpha are the most marked and measurements of its blood levels and computation of the PGF2 alpha/PGE coefficient may help assess the bronchial hyperreactivity without resorting to provocative tests.
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PMID:[Metabolic aspects of bronchial hyperreactivity to physical exertion in bronchial asthma]. 263 Dec 41

The role of prostaglandins in mediating angiotensin effects on autonomic neurotransmission was assessed. This was accomplished by examining the angiotensin-induced production of prostaglandins (PGE) and suppression of non-adrenergic (purinergic) neurotransmission in the presence and absence of cyclo-oxygenase inhibitors. The vas deferens of the rabbit was utilized for these studies because this preparation has a predominant non-adrenergic neurogenic component. Both angiotensins II and III enhanced PGE production and reduced non-adrenergic neurogenic contractions in a concentration-dependent manner from 1 to 1000 nM. Furthermore, indomethacin (2.8 microM) and eicosatetraynoic acid (10 microM) eliminated the inhibitory effect of the angiotensins on non-adrenergic neurotransmission. However, acetylsalicylic acid (10 microM) prevented the production of PGE in response to the angiotensins but failed to alter the suppression of non-adrenergic neurotransmission. The latter data are inconsistent with the hypothesis that PG's mediate angiotensin-induced depression of non-adrenergic neurotransmission. The mechanism by which indomethacin and eicosatetraynoic acid prevent angiotensin effects on non-adrenergic neurotransmission was not elucidated but previous reports suggest that these agents may act as angiotensin receptor antagonists. All of the cyclo-oxygenase inhibitors examined tended to potentiate angiotensin effects on adrenergic neurotransmission.
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PMID:Prostaglandins do not mediate the inhibitory effects of angiotensins II and III on autonomic neurotransmission in the rabbit vas deferens. 284 51

Pharmacokinetic studies of five biological response modifiers (BRMs) show diverse regulator functions on effector cell responses and a capacity to cause the secretion of specific soluble factors. Of the five BRMs tested, MVE-2, Poly ICLC, OK-432, and alpha beta IFN were capable of stimulating both natural killer (NK) cell and macrophage (M phi) tumoricidal activity, whereas BM 41-332 augmented only NK cells. Following one treatment with the aforementioned BRMs, M phi activity remained elevated for a longer period (10-14 days) than did NK cell activity (6-9 days). Of particular interest, multiple treatment with BRMs led to a downregulation of NK cell activity (hyporesponsiveness). Three soluble secretory products were induced by these BRMs (colony stimulating factor, CSF; prostaglandin E, PGE; and interferon, IFN). Treatment with MVE-2 and Poly ICLC led to a significant increase in bone marrow cellularity and GM-CFV-C. Results of studies with the cyclo-oxygense-inhibited indomethacin indicate that CSF and PGE are produced and/or secreted by different cellular mechanisms. The depression of effector cells (NK, bone marrow, and GM-CFU-C), as the result of cyto-reductive treatment with cyclophosphamide, could be reversed by treatment with MVE-2. A significantly earlier time to recovery of these effector cells was achieved following MVE-treatment. When MVE-2 was used as an adjuvant to initial tumor cyto-reductive chemotherapy, more successful antitumor response was achieved, indicating that MVE-2 functioned to elevate a substantial effector cell response as well as reconstituting bone marrow cellularity.
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PMID:Biological response modifiers: regulators of the cellular immune system and adjuvants in antitumor therapy. 348 34

Fifty-two steroids, structurally related to spironolactone, were tested for their ability to alter excretion of urinary prostaglandin-E metabolites (U-PGE-M). We found that steroids which are associated with elevation or depression of blood pressure will elevate or depress basal levels of U-PGE-M in the rat. Structural requirements for elevation or depression of metabolites are narrow and sensitive to slight conformational changes in either the C-17 side chain or the steroid nucleus. Metabolite-elevating steroids share a common basic conformation, and metabolite-depressing steroids share a different common basic conformation. These two basic conformations differ chiefly in the C-17 side chain. The conformational requirements are analogous to the specificity shown by hormone receptors or by enzymes. A strong association of urine volume with U-PGE-M (r = -0.93) was demonstrated in rats treated with spironolactone. A possible explanation relating these results to alteration of blood pressure was presented.
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PMID:Specificity and structural relationships of steroids which affect phospholipase/prostaglandin synthetase, in vivo: a possible relation to blood pressure. 392 68


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