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)

Cyclic AMP and its dibutyryl derivative inhibit neuronal firing of the labellar sugar sensitive receptor of the blowfly when applied in conjunction with the stimulant sucrose. Furthermore, simultaneous application of aminophylline (phosphodieterase inhibitor) and sucrose or in combination with cyclic AMP caused a similar depression of the sugar receptors response. In contrast, dibutyryl cyclic GMP elicited an increase in sugar receptor firing when applied with sucrose to sugar receptor. Either 5'-AMP or 5'-GMP in combination with sucrose had no discernable effect on the sugar receptors response. Different ratio combinations of cyclic AMP and dibutyryl cyyclic GMP showed the striking inhibitory effect of cyclic AMP upon the dibutyryl cyclic GMP elicited increases in receptor firing frequency. Therefore, it is suggested that these two nucleotides may be mediating different but complimentary aspects of sugar receptor function in a push-pull manner.
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PMID:Apparent opposing effects of cyclic AMP and dibutyryl cyclic GMP on the neuronal firing of the blowfly chemo-receptors. 18 Oct 76

Stimulated rabbit peritoneal polymorphonuclear leukocyte (PMN) preparations simultaneously produce prostaglandin-like material and mediators that induce metabolic alterations in experimental animals characteristic of the host's responses to inflammation. The alterations observed in rats include responses by: proteins, carbohydrates, hormones, trace metals, and total blood neutrophils. This study demonstrates a possible relationship between prostaglandins and PMN-derived substances that mediate plasma zinc depression, hepatic amino acid uptake, and increased numbers of blood neutrophils. Production of these mediators by stimulated-PMN preparations was prevented by 23 muM indomethacin or 93 muM aspirin. Conversely, morphine (2 mM or less) had no detrimental effect on production of these mediators, although, it consistently stimulated production of a substance stimulating total blood neutrophia. In addition, 2 muM prostaglandin E and F stimulated production of substances mediating hepatic amino acid uptake plasma zinc depression, respectively. At this concentration, neither prostaglandin significantly altered production of substances mediating increased numbers of total blood neutrophils. A partial-nitrogen atmosphere, dibutyryl cyclic analogs of AMP and GMP, or homogenization of the PMN had no effect on mediator production. The inhibitory effect of indomethacin and aspirin also was observed with PMN-homogenastes. These experimental observations suggest that prostaglandin synthesis has a function in production of mediators by stimulated-PMN preparations.
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PMID:Possible relation of prostaglandins to PMN-derived mediators of host metabolic responses to inflammation. 19 Jun 50

The action of 21 purine compounds on the twitch response of the electrically stimulated guinea pig isolated ileum has been investigated. Adenosine and related compounds produced a dose-dependent depression of the response. Adenosine was the most potent and 2'-deoxyadenosine had one hundredth the potency of adenosine. Adenine, hypoxanthine, inosine, IMP, ITP, xanthine, xanthosine, XMP, XTP, guanine, GMP and GTP were ineffective at concentrations less than 1 mM. Adenosine (30 microgram) reduced the electrically induced ACh output from the ileal strips. The dose--depression curve for adenosine (0.1--30 microgram) was shifted to the right in the presence of xanthine derivatives and of these, theophylline was the most potent inhibitor of adenosine. On the other hand, dipyridamole (0.1--1 microgram) and hexobendine (0.1--1 microgram) shifted the curve to the left. They markedly inhibited 3H-adenosine uptake into the ileum. Theophylline (0.1 mM), dipyridamole (0.3 microgram) and hexobendine (0.3 microgram) did not affect tetrodotoxin-, adrenaline-, strychnine- and morphine-induced inhibition of the twitch response. The present investigations have revealed that adenosine and related compounds reduce ACh release from the intramural cholinergic nerves in the guinea pig ileum possibly in a specific manner (or through a specific receptor site) different from that of other inhibitors such as morphine.
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PMID:Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. 63 57

1. The effects of dibutyryl guanosine 3',5'-cyclic monophosphate (db-cyclic GMP) were studied in vitro on calcium channels of neurones in rabbit vesical parasympathetic ganglia, using intracellular and single-electrode voltage-clamp recordings. 2. Db-cyclic GMP (100 microM) caused membrane depolarization associated with a decrease in membrane input resistance and an after-hyperpolarization associated with an increase in membrane input resistance. 3. Db-cyclic GMP (0.01-1 mM) caused a concentration-dependent, transient inward current followed by a long-lasting outward current. Membrane conductance was increased and decreased during the inward and outward currents, respectively. 4. The db-cyclic GMP-induced inward current was depressed in nominally calcium-free solutions, by cobalt (1 mM) and nicardipine (10 microM). The mean reversal potentials of the inward current were +42 and -20 mV in the presence and absence of calcium in the external solution, respectively. 5. The db-cyclic GMP-induced inward current was not altered by lowering the external sodium concentration, raising external potassium concentration or by intracellular injection of caesium. 6. A calcium-insensitive component of the db-cyclic GMP-induced current was increased by lowering the external chloride concentration and blocked by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid, a chloride channel blocker. 7. Voltage-dependent, high-threshold calcium currents were depressed during the db-cyclic GMP-induced inward current and facilitated during the outward current. 8. Cyclic GMP was less potent than db-cyclic GMP in causing both inward and outward currents or modulation of calcium currents. GTP, GDP, GMP, guanosine, 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin did not alter the holding current or voltage-dependent calcium currents. 9. It is concluded that intracellular cyclic GMP causes not only activation of resting calcium and chloride channels but also a transient depression followed by long-lasting facilitation of voltage-dependent calcium currents in neurones of vesical parasympathetic ganglia.
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PMID:Guanosine 3',5'-cyclic monophosphate regulates calcium channels in neurones of rabbit vesical pelvic ganglia. 133 64

1. The aim of this investigation was to study the relationship between contractile responsiveness, activation of the L-arginine pathway and tissue levels of guanosine 3':5'cyclic monophosphate (cylic GMP) in aortic rings removed from rats 4 h after intraperitoneal administration of bacterial endotoxin (E. coli. lipopolysaccharide, LPS, 20 mg kg-1). 2. LPS-treatment resulted in a reduction of the sensitivity and maximal contractile response to noradrenaline (NA). 3. Depression of the maximal contractile response was restored to control by 6-anilo-5,8-quinolinedione (LY 83583, 10 microM), which prevents activation of soluble guanylate cyclase. 4. Cyclic GMP levels in tissue from LPS-treated rats were 2 fold greater than cyclic GMP levels detected in tissue from control (saline-treated) rats. The LPS-induced increase in cyclic GMP content was observed both in the presence and absence of functional endothelium. 5. Addition of L-arginine 1 mM) to maximally contracted aortic rings produced significantly relaxation of rings from LPS-treated rats but not rings from control animals. In the LPS-treated group, addition of L-arginine was also associated with a significant increase in cyclic GMP content. L-Arginine had no effect on the cyclic GMP content of control rings. D-Arginine (1 mM) was without effect. 6. In rings from LPS-treated rats, NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of nitric oxide (NO) production, increased the contractile response to NA and prevented the LPS-induced increase in cyclic GMP content. In control rings, L-NAME increased the NA sensitivity only when the endothelium remained intact and reduced the cyclic GMP content of these rings to that of control endothelium-denuded rings. 7. These results demonstrate that LPS-induced hyporeactivity to NA occurs secondarily to activation of the L-arginine pathway and subsequent activation of soluble guanylate cyclase in vascular tissue. In addition they suggest that LPS induces the production of an NO-like relaxing factor in non-endothelial cells.
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PMID:Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. 167 81

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.
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PMID:Pharmacology and therapeutic effects of nicorandil. 215 May 92

Cyclic GMP depresses Ba2+ current through high-voltage-activated Ca2+ channels (ICa) in acutely isolated hippocampal neurons. The effect is produced by intra-, but not extracellular, cGMP or by 5' GMP. The membrane-permeant derivative, 8-Br-cGMP, produces a reversible suppression. The effect of 8-Br-cGMP is similar to phorbol ester-induced ICa depression, except that ICa depression due to 8-Br-cGMP is not blocked by protein kinase inhibitors H-8 or H-7, whereas phorbol ester effects are. The data suggest that cGMP depresses ICa by a cGMP-kinase- and protein kinase C (PKC)-independent mechanism. Cyclic AMP, which enhances ICa, and the cyclic nucleotide phosphodiesterase inhibitor, IBMX, both antagonize ICa depression induced by 8-Br-cGMP, but not that due to phorbol esters. Cyclic IMP, a more potent activator of phosphodiesterase than of cGMP-dependent protein kinase, is also a powerful depressant of ICa. We conclude that cGMP-induced depression of ICa is mediated by activation of cyclic nucleotide phosphodiesterase with consequent reduction of intracellular cAMP.
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PMID:Cyclic GMP depresses hippocampal Ca2+ current through a mechanism independent of cGMP-dependent protein kinase. 285 1

Following previous demonstration that isoproterenol stimulated and norepinephrine inhibited gastric acid secretion induced by secretagogues, role of adrenergic agonists was studied by measuring acidity the peptic activity of the effluent of the perfused rat stomach. Response of gastric secretion to isoproterenol was increased by theophylline treatment but was not affected by metiamide treatment. N6, O2'-Dibutyryladenosine 3', 5'-cyclic monophosphoric acid sodium salt monohydride (dibutyryl-c-AMP) stimulated gastric secretion in a dose-dependent manner. These results suggest the possibility that the action of isoproterenol in gastric acid secretion is mediated by c-AMP. However, gastric secretion induced by pentagastrin, histamine, or carbamylcholine was not affected by theophylline treatment. N2, O2'-Dibutyrylguanosine 3', 5'-cyclic monophosphoric acid sodium salt (dibutyryl-c-GMP) did not exert any effect on gastric secretion. Depression of pentagastrin-induced gastric secretion by norepinephrine was reversed by EGTA infusion. Moreover, Ca2+, depressed pentagastrin-induced gastric secretion. These results suggest that the action of norepinephrine is closely related to the concentration of Ca2+.
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PMID:Role of adrenergic agonists on gastric secretion in the rat. 611 Jul 14

In the transversely cut rat hippocampus, adenosine caused a dose-dependent increase in the accumulation of [3H]cyclic AMP from [3H]ATP. Adenosine breakdown products were inactive. AMP was somewhat less effective than adenosine, and its effect could be partially, but not completely, abolished by alpha, beta-methylene-ADP and GMP, which inhibited its metabolism by 5'-nucleotidase. The effect of adenosine was unaffected by inhibitors of adenosine deaminase, but enhanced by several inhibitors of adenosine uptake. Some analogues of adenosine, including N6-phenylisopropyladenosine (PIA), 2-chloroadenosine and adenosine 5'-ethylcarboxamide (NECA), were more active than adenosine, whereas others such as 2-deoxyadenosine and 9-(tetrahydro-2-furyl)adenine (SQ 22536) actually inhibited the response. The effect of PIA was highly stereospecific. The action of adenosine was inhibited by several alkylxanthines, the most potent of which was 8-phenyltheophylline. [3H]Cyclohexyladenosine (CHA) bound specifically to cell membranes from the rat hippocampus. The extent of binding was similar to that found in other cortical areas. The relative potency of some adenosine analogues and alkylxanthines to displace labelled CHA was essentially similar to their potency as effectors of the cyclic AMP system. Adenosine contributed to the cyclic AMP-elevating effect of alpha-adrenoceptor-stimulating drugs and several amino acids, but not to that seen with isoprenaline. The cyclic AMP increase seen following depolarization was only partially adenosine-dependent. The present results demonstrate that the rat hippocampus contains adenosine receptors mediating cyclic AMP accumulation and that these receptors have similar characteristics to those mediating pyramidal cell depression. Adenosine-induced cyclic AMP accumulation may be used as a biochemical correlate to electrophysiology and as a convenient parameter to assess the influence of drugs on adenosine mechanisms in the rat hippocampus.
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PMID:Adenosine receptors mediating cyclic AMP production in the rat hippocampus. 612 48

Parathyroid hormone (PTH) and calcitonin exert well known effects on the renal tubule which are thought to involve specific hormone receptors and adenyl cyclase. In the intestine, it is not clear whether the action of PTH and calcitonin is only indirect or also direct, and their mechanisms of action are much less well established. In the present study, possible direct effects of PTH and calcitonin on Na+ transport in isolated intestinal epithelial cells of rats were investigated. In the presence of bovine PTH (1.2 I.U/ml) in the incubation medium, the Na+ efflux rate constant (oKNa) of isolated enterocytes was significantly reduced when compared to that in control experiments with the hormone vehicle only. The mean depression of oKNa induced by bovine PTH was 26% as compared to the control (100%) and to that induced by ouabain (4.0 mM) which was 44%. No depressant effect of bovine PTH on oKNa was observed when the isolated enterocytes were incubated with ouabain (4.0 mM). Thus, bovine PTH appeared to inhibit the ouabain-sensitive Na+ pump. When incubating the isolated epithelial cells in an EGTA-containing CA2+-free medium, bovine PTH lost its capacity to inhibit oKNa. Thus, the presence of extracellular Ca2+ appeared necessary for the inhibitory effect of bovine PTH. In contrast to its effect on oKNa, bovine PTH induced no change in net Na+ uptake by isolated enterocytes. Moreover, no significant effect on enterocyte Na+ transport could be demonstrated for salmon or porcine calcitonin at two different concentrations in the incubation medium, Neither bovine PTH nor salmon calcitonin induced significant changes in enterocyte cyclic AMP or cycle GMP concentrations. It was concluded that bovine PTH, but not calcitonin, exerted a directed inhibitory effect on the ouabain-sensitive oKNa of isolated rat enterocytes. The effect of bovine PTH occurred without measurable activation of the cyclic nucleotide system but needed the presence of Ca2+ in the incubation medium to be operative.
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PMID:Rat enterocyte Na+ transport in vitro. Action of parathyroid hormone and calcitonin. 627 49


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