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)

This study examines the possible role of endogenous prostaglandins (indomethacin; PGF2a; PGE1; PGE2; and prostacyclin or PGI2) on the spontaneous motility of the human ampullar and isthmus deprived of the mesosalpinx. Fallopian tubes were obtained from 12 patients who had hysterectomy and salpingo-oophorectomy. The segments of the tubes were prepared for contractile recordings as previously described and divided into 2 groups: 1) ampullar and isthmic segments were followed by spontaneous variations in motility during 30 minutes; and 2) cumulative close-response curves for PGI2 were constructed for ampullar and isthmic segments 30 minutes after the end of equilibrium. Contractile functions were evaluated in terms of amplitude of isometric developed tension (IDT) and frequency of contraction, and when pertinent, changes in resting basal tone. Student's t-test was used for statistical analysis, and differences between means were considered significantly at P=0.05 or less. Indomethacin significantly enhance the IDT of the isthmic but not the ampullar region. However, a single and identical concentration of 10-6M of PGE1 and PGI2 depressed the ampullar while PGE2 and PGF2a enhanced its contractions. In the isthmus, PGE1, PGE2 and PGF2a augmented while PGI2 diminished the IDI. Both ampullar and isthmic regions exhibited a dose-dependent depression of IDI and contractile frequency. In the isthmus, PGI2 produced a biphasic action on resting basal tone while in the ampulla, only a progressive dose-dependent decline was seen. Prostacyclin may be synthesized by the isthmic region of the human fallopian tubes, but whether it occurs in vivo or what its physiological significance is remains to be seen.
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PMID:Spontaneous motility of isolated mesosalpinx-free isthmic and ampullar segments from human oviducts, and the influences of indomethacin and prostacyclin (PGI2). 4 1

The pesticide chlordimeform (CDM) depressed the electrically-induced twitch responses of the guinea pig longitudinal muscle ED50 = 3 X 10(-5)M). Naloxone reversed twitch depression induced by morphine but not by CDM. Phentolamine reversed twitch depression induced by either norepinephrine or clonidine, but not by CDM. PGE2 completely reversed twitch depression induced by either CDM or indomethacin, but only partially reversed twitch depression induced by lidocaine. The actions of CDM best resemble those of the nonsteroidal anti-inflammatory agents. The reversibility of the CDM depression by washing indicates that the guinea pig ileal preparation is a convenient screen for distinguishing reversible from irreversible inhibitors of prostaglandin biosynthesis.
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PMID:Reversible depression of electrically-induced contractions of guinea pig longitudinal muscle by a reversible inhibitor of prostaglandin synthetase. 12 9

Ticlopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3',5'-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment. These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.
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PMID:Mode of action of ticlopidine in inhibition of platelet aggregation in the rat. 22 22

Exposure of cultured Graafian follicles to PGE2 for 20 h resulted in a loss of the cyclic AMP response to fresh hormone. This desensitization was prevented by addition to the medium of D2O (25--50%) or Li+ (0.6--6 mM), agents believed to stabilize microtubules, as well as by phalloidin (1.0--10 microM), believed to stabilize the polymerized state of actin, in a dose-dependent manner. The spontaneous recovery of responsiveness to PGE2 upon incubation of refractory follicles for 6 h in hormone-free medium was prevented by addition to the medium of cytochalasin B (CB; 3 microgram/ml) or of the actin-binding myosin subfragment HMM S-1 (80 microgram/ml) or of anti-actin serum; viz. by agents likely to interfere with microfilament function. D2O (50%) caused morphological damage to the inner layer of the membrana granulosa and severe depression of protein synthesis. The other drugs used (phalloidin, LiCl and cytochalasin B) had no such effects. Resensitization of refractory follicles was also prevented by cycloheximide (10 micrograms/ml) and by actinomycin D (10 micrograms/ml). It is speculated that the recovery process may involve the insertion of a newly synthesized protein, such as PG-receptor, into the membrane by a mechanism dependent on microfilament action. These findings provide suggestive evidence for the hypothesis that cytoskeletal elements associated with the cell membrane take part in the modulation of the adenylate cyclase response to hormones.
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PMID:Effect of modulators of cytoskeletal function on desensitization and recovery of PGE2-responsive ovarian adenylate cyclase. 23 63

Implants of crystalline PGE2 in the basal preoptic-anterior hypothalamic areas stimulates high levels of sexual receptivity in ovariectomized, estrogen-primed rats. Indomethacin, which blocks the synthesis of PGE2 failed to inhibit either estrogen- or estrogen plus progesterone-induced receptivity. Neither intracerebral nor subcutaneous administration of indomethacin diminished the display of steroid induced reproductive behavior without also causing a depression in open-field activity, and in some cases, causing gastrointestinal problems and even death. These results suggest the prostaglandin synthesis is not a required step in the mechanism by which estrogen and progesterone exert their behavioral effects. The possibility that PGE2 and LH-RH synthesis and/or release might contribute to a collateral mechanism for the induction of sexual receptivity was discussed.
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PMID:Effects of prostaglandin synthesis inhibitor, indomethacin on estrogen- and estrogen plus progesterone-induced sexual receptivity in ovariectomized rats. 67 64

The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin (Indo) were studied on isolated detrusor smooth muscle strips in balanced salt solution and in 80 mMK+ depolarizing solution. The addition of Indo to the smooth muscle preparation at concentrations of 0.1 to 1.0 micronM produced depression of spontaneous motility that was partially antagonized by PGE2 or by elevating the extracellular Ca2+ level. Alone, both PGE2 and Ca2+ caused a marked increase in motility, increasing both frequency and amplitude. In low Ca2+, K+ depolarized bathing medium with 0.1 mM EGTA added PGE2 or PGF2alpha augmented Ca2+ contractures both in velocity and amplitude while either PG without Ca2+ had no effect on the smooth muscle. Indo produced a noncompetitive antagonism of the Ca2+ dose response curve in 80 mM K+ depolarized preparations suggesting a direct effect on Ca2+ flux. Also Indo depressed both PG and Ca2+ contractures in terms of velocity and magnitude, suggesting that Indo may act at Ca2+ channels in addition to its action on PG synthetase. These data support the work of others who suggest that PGs may augment Ca2+ permeability, acting at the Ca2+ channel or as a carrier for Ca2+ across smooth muscle cell membranes.
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PMID:Interactions of calcium, prostaglandins and indomethacin on the smooth muscle of the bladder. 67 49

Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypertension was induced by unilateral nephrectomy, followed by the administration of DOCA and the elevated sodium diet. The treatment was short in one group, long in the other, and both groups were compared to a control hypertensive group which received no treatment at all. Arachidonic acid worsened the experimental hypertension by 37% in the long treatment, and by 25% in the short treatment. The administration of lysine-acetylsalicylate diminished this hypertension. A non-saturated acid, oleic acid, which is not involved in prostaglandin synthesis, has no action. The authors would like to emphasize that in one of the previous experiments, L-tyrosine, the precursor of catecholamines, diminished the experimental hypertension in the rat, and also that L-DOPA and IMAO (MAOI) have comparable effects. It seems, therefore, that the depression of the central catecholaminergic activity, which is supposed to be the action of arachidonic acid via an increase in the PGE2 synthesis, appears to increase hypertension. It is noteworthy that the medial forebrain bundle (MFB) is catecholaminergic and that the periventricular system (PVS) is cholinergic. Thus hypertension may represent the peripheral vascular response to anguish which results from the activation of PVS and from the depression of MFB.
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PMID:The action of arachidonic acid on experimental hypertension in the rat. 112 60

The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-1 (IL-1) plays on the immunoregulation, and its ability to mimic various features of clinical malaria, reports on IL-1 in malaria are lacking. We found that only 2 out of 35 subjects with acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T-lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72 h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 +/- 2,900) and P. vivax malaria (13,000 +/- 3,300), as compared to that of healthy individuals (27,000 +/- 3,000). Addition of IL-1 partially reversed depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.
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PMID:Cytokines and dysregulation of the immune response in human malaria. 134 9

Adherence to extracellular matrix proteins modulates the functional and secretory activities of mononuclear phagocytes, although the mechanisms regulating these adherence-dependent changes are poorly understood. In this study, the ability of rat inflammatory peritoneal macrophages (PM) to adhere to an endothelial cell-derived extracellular matrix or a denatured collagen/fibronectin-coated surface and perform antibody dependent cell cytotoxicity (ADCC) and secrete reactive oxygen intermediates was compared with PM adherent to tissue culture plastic. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), two major cyclooxygenase products released by inflammatory macrophages, were also measured by PM adherent to the protein coated surfaces. Rat exudate PM were equally adherent to tissue culture plastic or wells coated with either endothelial cell derived matrix or denatured collagen (gelatin)/fibronectin. PM adherent to a denatured collagen/fibronectin-coated wells demonstrated significantly less cytolytic activity (15 +/- 2% lysis) when compared with either tissue culture plastic adherent PM (43 +/- 7% lysis) or PM adherent to extracellular matrix (59 +/- 11% lysis). PM adherent to extracellular matrix released twofold more TxB2 than plastic adherent PM, while PM adherent to denatured collagen/fibronectin released 40% more PGE2 than cells adherent to tissue culture plastic or 80% more PGE2 than PM adherent to the extracellular matrix. PM adherent to denatured collagen/fibronectin release less superoxide anion (27 +/- .9 nmoles/10(6) PM) than PM adherent to either tissue culture plastic (43 +/- 1 nmoles/10(6) PM) or the extracellular matrix (60 +/- 0.5 nmoles/10(6) PM). Furthermore, incubation of plastic adherent PM with exogenous PGE2 reduced superoxide production in a dose-dependent manner. These results demonstrate that the inhibition of ADCC and secretion of reactive oxygen intermediates by PM adherent to a denatured collagen/fibronectin surface correlated with an increased release of the immunosuppressive prostanoid PGE2. Furthermore, the addition of exogenous PGE2 to plastic adherent PM reproduced the depression in ADCC and superoxide anion production observed by PM adherent to a denatured collagen/fibronectin surface. These studies suggest that the increased production and release of PGE2 by inflammatory macrophages adherent to a denatured collagen surface may act to suppress cytotoxic mechanisms and thereby constitutes part of an autocrine feedback mechanism regulating macrophage function during wound injury.
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PMID:Surface contact modulation of inflammatory macrophage antibody dependent cytotoxicity and prostanoid release. 166 Aug 99

Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated. Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight). Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later. Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours. Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release. Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice. Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage.
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PMID:Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. 173 52


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