Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cyclic nucleotides on the proliferation of cultured T-lymphocytes (CTC) stimulated by either phytohemagglutinin (PHA) or lectin-free interleukin-2 (IL-2) were studied. The addition of either N6,O2-dibutyryl cyclic AMP (DB-cAMP), aminophylline or isoproterenol to CTC cultures significantly suppressed the proliferation of CTC stimulated by either PHA or IL-2. This inhibitory effect was maximal when added at initiation of the assay; however, significant depression was still observed when added 24 h later. When DB-cAMP and aminophylline were added together, the inhibitory effects were additive. When DB-cGMP was added to the CTC cultures, inhibition of both PHA- and IL-2-stimulated cultures was also found, but the degree of activity was considerably less than for DB-cAMP or aminophylline. In contrast, when carbachol was added, no inhibition or modulation in proliferation was seen. Lastly, DB-cGMP was not found to antagonize the inhibitory effect of DB-cAMP, but instead to further increase the level of inhibition. In summary, these studies illustrate that cyclic nucleotides modulate the proliferation of IL-2-stimulated CTC as well as PHA-treated cells. This model system should provide an approach to study, in more depth, the mechanism by which cyclic nucleotides or their inducers can modulate the latter stages of the lymphocyte proliferative response, which is mediated by the lymphokine, IL-2.
 ...
PMID:The effects of cyclic nucleotides on the proliferation of cultured human T-lymphocytes. 609 9

The acetylcholine (ACh) stores of cholinergic neurons of the myenteric plexus of guinea-pig ileum were labelled by preincubation with 3H-(methyl)-choline. The secretion of labelled transmitter evoked by electrical field stimulation at 1 Hz in the presence of eserine increased by 55% after addition of 0.5 mM 8-Br adenosine 3', 5'-cyclic monophosphate (8-Br cAMP). Atropine further enhanced the secretory response, but not more than in the absence of 8-Br cAMP. 8-Br guanosine 3', 5'-cyclic monophosphate (8-Br cGMP, 0.5 mM) did not change the secretory response to 0.5 or 1 Hz stimulation, either at 1.8 mM or at 0.6 mM calcium, in the absence of eserine. Nor did 1 mM 8-Br cGMP alter the effects of atropine or of oxotremorine. Activation of guanylate cyclase by 0.1 mM N-methyl-N'-nit-ro-N-nitroso guanidine failed to alter the secretory response to 0.5 Hz stimulation in the absence of eserine, or to influence the depression of the secretion caused by oxotremorine. The phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (a mM) neither altered the secretory response in the presence of eserine, nor the enhancing effect of atropine. The results suggest that cyclic nucleotides are probably not critically involved as "second messengers" in the muscarinic "autoinhibition" of ACh secretion from cholinergic myenteric neurons of guinea-pig ileum.
 ...
PMID:Secretion of 3H-acetylcholine from guinea-pig ileum myenteric plexus is enhanced by 8-Br adenosine 3', 5'-cyclic monophosphate but not changed by 8-Br guanosine 3', 5'-cyclic monophosphate. 618 55

We have compared the effects of cellular cyclic AMP modulation on the regulation of lipoprotein lipase in cultures of rat epididymal pad preadipocytes and mesenchymal heart cells. Addition of dibutyryl cyclic AMP (dibutyryl cAMP) or 3-isobutyl-1-methylxanthine (IBMX) to preadipocytes grown in serum-containing culture medium resulted in a progressive decrease in lipoprotein lipase activity released into the culture medium so that at 6-8 h enzyme activity ranged between 20 and 30% of that recovered in the control dishes. Similar short-term (6-8 h) studies of the heart cell cultures showed a variable and much less pronounced depression of lipoprotein lipase activity. Thus, following dibutyryl cAMP and IBMX treatment, lipoprotein lipase activity ranged between 70 and 95% of control values. Incubation for 6 h with cholera toxin was followed by a 4-fold rise in the concentration of cellular cyclic AMP in both types of culture, but while in heart cell cultures enzyme activity was unchanged, lipoprotein lipase activity in preadipocytes decreased to 30% of control value. After 24 h incubation with all three effectors, an increase in lipoprotein lipase activity was seen. In the preadipocytes the increase ranged between 50 and 150% above control value, in the heart cell cultures it was 100-250%. 24-h incubation of heart cell cultures with dibutyryl cAMP resulted in a 6-fold increase of heparin-releasable lipoprotein lipase activity while residual activity was doubled. The rise in surface-bound lipoprotein lipase was evidenced also by an increase in the lipolysis of chylomicron triacylglycerol. In the presence of cycloheximide, the dibutyryl cAMP-induced heparin-releasable and residual lipoprotein lipase activity declined at the same rate as the basal activity. The reason for the difference in response of cultured preadipocytes and heart cells to the effectors during the first 8 h of incubation has not been elucidated, but could be related to a possible absence of hormone-sensitive lipase in the heart cells, and hence in a difference in intracellular metabolism of triacylglycerol. On the other hand, a common mechanism can be postulated for the long-term effect of cyclic AMP on the induction of lipoprotein lipase activity in both types of cultures. It probably involves mRNA and protein synthesis, which culminates in an increase in enzyme activity.
 ...
PMID:Modulation of lipoprotein lipase activity in cultured rat mesenchymal heart cells and preadipocytes by dibutyryl cyclic AMP, cholera toxin and 3-isobutyl-1-methylxanthine. 618 19

The influence of histamine on the level of cyclic AMP was studied in human platelets. A dose-related accumulation of cyclic AMP was obtained, culminating at about 10 microM of histamine. The response was blocked by the H2 antagonist cimetidine, but neither by H1 antagonists nor by alpha- or beta-adrenergic antagonists. The results suggest that histamine causes an accumulation of cyclic AMP in human platelets by stimulation of H2 receptors. Cyclic AMP accumulation is supposed to be associated with a depression of the platelet function, and a reduced platelet release reaction was actually demonstrated by our results.
 ...
PMID:Histamine H2 receptor-mediated cyclic AMP formation in human platelets. 624 70

The effect of potassium ions on the formation of adenosine 3',5'-monophosphate (cAMP) in the rat cerebral cortex in vivo was studied under conditions where development of spreading depression had been blocked by pretreatment of the cerebral cortex by topically applied magnesium ions. A linear relationship between potassium concentrations applied to the cortical surface and levels of cAMP has been found. Moreover, potentiation of the K+-effect by magnesium ions has been observed.
 ...
PMID:May K+ ions stimulate the formation of cyclic AMP in the brain independently on their depolarizing action? 625 33

The acute in vitro actions of two potent melanocytolytic agents, hydroquinone (HQ) and beta-mercaptoethanolamine (MEA), were determined in the B-16, Cloudman S-91 and Harding-Passey (HP) murine melanomas grown in vivo. Drug treated melanoma dice (5--480 min) were analyzed for tyrosinase activity and cyclic nucleotide levels (cAMP, cGMP). HQ and MEA effects on tyrosinase activity are complex and vary with tumor type, duration of treatment and agent tested. MEA or HQ inhibited B-16 tyrosinase activity. With combined drug therapy, low concentrations of MEA plus HQ stimulate B-16 tyrosinase activity while high concentrations of the drugs have little effect on enzymatic activity. MEA depresses tyrosinase activity while HQ elevates enzymatic activity in the S-19 melanoma. Both high and low concentrations of the combined drugs (MEA plus HQ) elicit the same response, stimulation at 10 min followed by continued depression of tyrosinase activity for the remainder of the 4 h study period. MEA initially stimulates HP tyrosinase activity followed by depression of enzymic activity. In contrast, HQ initially depresses HP tyrosinase activity followed by stimulation of enzyme activity. In combination the drugs inhibit HP tyrosinase activity. The effects of MEA and/or HQ on murine melanoma cyclic nucleotide levels are equally complex. MEA or HQ elevate cAMP and cGMP levels in all three tumors with the exception of S-91 cGMP levels which are not altered. In combination the drugs increase cyclic nucleotide levels in each of the three tumor types but at different times. No correlation is present between cyclic nucleotide levels and tyrosinase activity. Thus, the action of increased cyclic nucleotide levels in melanogenesis can not be separated from the direct actions of MEA and HQ upon melanogenesis. The divergent effects of MEA and/or HQ on tyrosinase activity and cyclic nucleotide levels in these melanomas are not correlated with the known in vivo melanocytolytic activity of these drugs. Thus, these parameters appear to be inadequate indicators of melanoma cell viability in chemotherapeutic screening of drugs effective in destroying malignant melanoma.
 ...
PMID:Acute effects of two melanocytolytic agents, hydroquinone and beta-mercaptoethanolamine, upon tyrosinase activity and cyclic nucleotide levels in murine melanomas. 625 89

Street opiate addiction produces a significant depression in the absolute number of total T lymphocytes in peripheral blood as measured by the ability of the lymphocytes to rosette sheep red blood cells (SRBC). Associated with the decrease in T cells, there is an increase in the absolute number of null lymphocytes but no significant changes in B lymphocytes or total white blood cell count. The T cell values for 2 different populations of addicts (n = 12 and 32) are 31.8% and 23.1%, whereas the null cell values are 51.1% and 57.6%, respectively. The values for comparable control populations (n = 18 and 10) are: T% = 70.7% and 67.4%, and null % = 9.2% and 14.5%. Self-reported use of marihuana does not significantly alter the distribution of cell populations. A 1- to 3-hr incubation of addicted-derived lymphocytes with 10(-6) to 10(-7) M Naloxone reverses both T cell depression and null cell increase by allowing the null cells to express SRBC receptors. Cyclic AMP and dibutyryl cyclic AMP can also convert the null cells to T cells. The conversion of null to T lymphocytes has additionally been measured by monitoring the increase in PHA-stimulated growth in 72-hr cultures as determined by tritiated thymidine incorporation into DNA. These results support the hypothesis that opiates can alter T lymphocyte number and function in vivo, and that this alteration may produce a significant degeneration in the immune competence of street opiate addicts.
 ...
PMID:Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: in vivo evidence for opiate receptor sites on T lymphocytes. 625 68

1. A study has been made of the decline in contractility and some associated metabolic changes which occur in the isolated frog ventricle during the development of hypodynamic depression. 2. The release of two identified prostaglandins (PG), E1 and E2, together with several as yet unknown prostaglandin-related substances (PRS), accompanies the development of hypodynamic depression. There is a close correlation between the extent to which the isometric twitch is depressed and the quantity of prostaglandin released into the superfusate. 3. Fractionation of extracts of 'used' superfusates, using preparative-scale thin-layer chromatography, revealed the presence of six major components, four of which (PGE1 and PGE2 and two unidentified components) were found to be cardioactive and potentiated contraction when tested subsequently on hypodynamic preparations. 4. Two agents which influence prostaglandin biosynthesis, arachidonic acid and indomethacin, are found to affect both the rate at which the hypodynamic state develops and the extent to which the 'steady-state' twitch tension is depressed, in a dose-dependent manner. Indomethacin, a PG-synthetase inhibitor, accelerates the decay and depresses the final 'steady-state' tension attained, whereas arachidonic acid, the principal precursor for prostaglandin biosynthesis, has the converse effects. 5. Measurements of endogenous 3'5'-cyclic nucleotide levels reveal a time-dependent decrease in intracellular adenosine 3'5'-cyclic monophosphate (3'5'-cyclic AMP) and a concomitant increase in guanosine 3'5' cyclic monophosphate (3'5'-cyclic GMP). The decline in isometric twitch tension is paralleled almost exactly by an equivalent reduction in the ratio 3'5'-cyclic AMP: 3'5'-cyclic GMP. 6. Superfusion of isolated ventricles with Ringer solution containing exogenous, lipid-soluble derivatives of 3'5'-cyclic AMP and 3'5'-cyclic GMP affects both the rate of decline of the isometric twitch and the steady-state tension ultimately reached: thus, 8-bromo-3'5'-cyclic GMP accelerates the decline in contractility and depresses the steady-state level, whereas dibutyryl 3'5'-cyclic AMP delays the development of hypodynamic depression, and elevates the final twitch tension. The effects of both 3'5' cyclic nucleotide derivatives are dose-dependent. 7. The possible involvement of prostaglandins and 3'5'-cyclic nucleotides as causal agents in the mechanism of hypodynamic depression is discussed. The biochemical basis for the implied antangonistic effects of 3'5'-cyclic AMP and 3'5'-cyclic GMP in regulating ventricular contractility is considered in the following paper (Flitney & Singh, 1980).
 ...
PMID:Release of prostaglandins from the isolated frog ventricle and associated changes in endogenous cyclic nucleotide levels. 625 39

Having previously established, that prostaglandins play a role in the regulation of the immune response to polyvinyl pyrollidone, a T-independent antigen, further investigations of the role of prostaglandins and cyclic nucleotides in the control of the immune response to polyvinyl pyrollidone were initiated. Strongly immunogenic (PVP 360,000) and weakly immunogenic (PVP 10,000) molecular sizes of polyvinyl pyrollidone were examined for their effects on splenic PGF2 alpha, PGE and cyclic nucleotide levels. The results show, that PVP 360,000 induces marked changes in PGF2 levels. There is an early marked depression at 2 hours after injection followed by an increase which peaks at 2 hour. At subsequent time intervals (9-10, 13-14 and 16-18 hour) high values were observed, especially in the latter case. cAMP levels undergo significant fluctuations, exhibiting very big rise at 12 and 13 hour post-immunization, cGMP levels are elevated at 2 hour declining thereafter. PGE level in C57Bl mice exhibits very substantial increase at 4-6 hour after immunization, in athymic mice, however, the increase was not significant and was preceded by a profound drop in PGE concentration. PGE level in the splenocytes from athymic mice shows a constant increase till 4 hour after PVP addition, followed by a little decrease at 6-7 hour. cAMP concentration in athymic mice exhibits a drop at 3-4 hour after immunization, followed by an increase at 5-6 hour post-immunization. Indomethacin, an inhibitor of prostaglandin synthetase, blocks the changes in PGF2 and cGMP level but has little effect on cAMP. In contrast, the weakly immunogenic form PVP 10,000 induces a large bimodal increase in cAMP levels peaking at 2 hour and again increasing between 6-8 hour; cGMP levels also rise, but more slowly. The increase in cAMP is blocked by indomethacin even though no comparable increases in PGF2 levels are observed. The changes induced by PVP 10,000 appear to be dependent on T cells since comparable changes are not observed in athymic mice. Although PVP 10,000 is non-immunogenic in normal mice or whole spleen cultures, it is immunogenic in athymic mice and purified B cell cultures. This difference has been traced to an apparent difference in the activation of T cells vs. B cells by PVP 10,000. Lastly, although inhibition of PG synthesis results in an enhancement of the immune response to PVP 360,000, no such enhancement is observed with PVP 10,000. The relevance of prostaglandin and cyclic nucleotide changes to the development of the immune response is discussed.
 ...
PMID:The regulation of the immune response to polyvinylpyrollidone: antigen induced changes in prostaglandin and cyclic nucleotide levels. 625 89

The hypokalemic response was roughly proportional to the dose of insulin. The hypokalemia due to adding insulin to galactose or fructose loading was slightly greater than that with insulin and glucose or mannose loading, suggesting a hexose stereospecificity of the response. When epinephrine (13.6 nmol/kg, i.v.) was given after one of the hexoses plus insulin, the hyperkalemia with glucose and galactose was 2.5-3 mEq/l, about twice that due to fructose or mannose. The hyperglycemia was about 2 mmol/l for glucose, 1 mmol/l for galactose, mannose, fructose, and ouabain with glucose, and 0.25 mmol/l for phloridzin with glucose. Addition of epinephrine, isoproterenol, and cAMP caused a significant depression of Na+,K+-ATPase activity in rat liver (P < 0.01) but the addition of insulin did not. These results show that there was a relation between the levels of blood glucose and serum potassium after an insulin-containing hexose infusion and that membrane permeability was stereospecific.
 ...
PMID:Effects of hexose infusion with insulin and of additional epinephrtine injection on the levels of serum potassium and blood glucose in dogs. 625 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>