Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.1.21 (CPT)
4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify differences in the operating mechanisms of adenosine receptor subtypes (A1 and A2), striatal extracellular dopamine levels under various conditions were determined by in vivo microdialysis. Adenosine (50 microM) as well as the selective A1 agonist, 2-chloro-N6-cyclopentyladenosine (CCPA; 1 microM) decreased striatal extracellular dopamine levels, while the selective adenosine A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT; 50 microM) and caffeine (100 microM) increased striatal extracellular dopamine levels. A selective A2a agonist, 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadeno sine (CGS21680; 10 microM), a selective A2 agonist, N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA; 5 microM) and a selective A2 antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 10 microM), did not affect extracellular dopamine levels. When the A1 receptor was blocked by CPT, extracellular dopamine levels were increased by adenosine and DPMA, decreased by caffeine as well as DMPX, and unaffected by CGS21680. These results indicate that the stimulatory effects of the A2 receptor on striatal extracellular dopamine levels are masked by the inhibitory effects of the A1 receptor.
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PMID:Adenosine A1 and A2 receptors modulate extracellular dopamine levels in rat striatum. 882 61

Energy deprivation, as a result of aglycemia, leads to depression of the central synaptic transmission. Endogenous adenosine has been implicated in this depressant effect. We have studied the possible involvement of endogenous adenosine in the depression of corticostriatal excitatory transmission induced by glucose deprivation by using intracellular recordings in brain slices. After stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny neurons. Adenosine (3-300 microM) or brief periods (5-10 min) of aglycemia reduced the EPSP amplitude but did not alter the membrane potential and the resistance of the recorded cells. These inhibitory effects were not associated with an alteration of the postsynaptic sensitivity to exogenous glutamate but were coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. A delayed postsynaptic membrane depolarization/inward current was detected after 15-20 min of glucose deprivation. The presynaptic inhibitory effects induced by adenosine and aglycemia were both antagonized either by the nonselective adenosine receptor antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 microM) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nM). Conversely, these antagonists affected neither the delayed membrane depolarization/inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1 mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1 receptors mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses, whereas ATP-dependent potassium channels do not play a significant role in this presynaptic inhibition.
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PMID:Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses. 916 11

The effects of adenosine (100 nM, icv), dipyridamole (DPM, 5 mg/kg, i.p.), adenosine A1 receptor antagonist 8-cyclopentyl-theophylline (8-CPT, 10 mg/kg, i.p.), and aminophylline (AMP) and caffeine (CAF) (at equivalent doses of 35 mg/kg, i.p.), were examined in rats. Anti-epileptic drugs (AEDs) were also administered i.p., viz, carbamazepine (CBZ, 10 mg/kg); phenobarbitone (PB, 10 mg/kg); phenytoin (PHT, 20 mg/kg); valproic acid (VPA, 300 mg/kg); and diazepam (DZP, 10 mg/kg), to study their effects on EEG after discharge (AD) and postictal depression (PID) induced by cortical stimulation. The AD parameters: (1) duration of EEG-AD (sec) and (2) number of spikes was noted both during pre and post drug treatment sessions. Adenosine and DPM had no special effects on AD parameters but showed significant prolongation of PID. All the adenosine antagonists, 8-CPT, AMP and CAF produced significant prolongation of AD duration, increase in number of spikes and reduced the duration of PID to a significant extent. Interestingly, some of the AEDs, viz. CBZ, VPA and DZP showed abolition of all the EEG-AD parameters whereas PB and PHT failed to show any significant effect. The results confirm previous findings on involvement of adenosine in postictal events.
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PMID:Influence of adenosine, dipyridamole, adenosine antagonists and antiepileptic drugs on EEG after discharge following cortical stimulation. 931 32

von Willebrand factor (vWF) is stored and released from endothelial secretory granules called Weibel-Palade (WP) bodies. Acute release can be induced by thrombin, histamine, and other mediators of thrombosis or inflammation. Their effect is thought to be mediated by an increase in intracellular free calcium ([Ca2+]i). Purine nucleotides such as adenosine triphosphate (ATP) and adenosine diphosphate (ADP) are released from platelet dense granules and from ischemic tissues and are important regulators of platelet function and vascular tone. In the present study, we investigated whether they could also induce exocytosis from cultured endothelial cells. ATP (1 to 100 micromol/L) induced a dose-related increase in vWF release, with a 2.3-fold maximal increase after 30 minutes. Similar responses were observed with ADP. ATP induced calcium mobilization from intracellular stores, an effect mimicked by 2-methylthio-ATP, a selective agonist for P2y receptors. However, 2-methylthio-ATP-induced vWF release was only 43% of the ATP response. ATP-induced vWF release was also associated with a twofold increase in cellular cyclic adenosine monophosphate (cAMP) content, and was potentiated by 3-isobutyl-1-methylxanthine ([IBMX] added to increase cAMP levels by blocking cellular phosphodiesterases) and 8-bromo-cAMP and inhibited by more than 50% by Rp-8-CPT-cAMPS, a competitive protein kinase A inhibitor. Adenosine but not 2-methylthio-ATP mimicked the ATP-induced increase in cAMP. ATP-induced vWF release was partly inhibited by adenosine deaminase, which degrades adenosine generated from ATP in the incubation medium. Adenosine (1 to 100 micromol/L) failed to induce vWF release, but potentiated the secretory response to 2-methylthio-ATP and thrombin without modifying the calcium response to these agents. Our results suggest that ATP/ADP can induce vWF release from endothelial cells via dual activation of P2y and adenosine A2 receptors. ATP/ADP-induced exocytosis could be involved in the regulation of thrombus formation and ischemia-reperfusion injuries. Further, we provide evidence that a receptor-mediated increase in cellular cAMP can potentiate the secretory response to calcium-mobilizing agents.
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PMID:Purine nucleotides induce regulated secretion of von Willebrand factor: involvement of cytosolic Ca2+ and cyclic adenosine monophosphate-dependent signaling in endothelial exocytosis. 941 75

We have investigated the effects of adenosine on the cardiovascular system of the Antarctic fish Pagothenia borchgrevinki. Continuous measurements of ventral and dorsal aortic blood pressures, heart rate (fh) and ventral aortic blood flow (cardiac output, q_dot ) were made using standard cannulation techniques and a single-crystal Doppler flowmeter. On line measurements of arterial P(O2) were made using an oxygen electrode connected to an extracorporeal loop. Adenosine (10 nmol kg(-)(1)) and the specific A(1)-receptor agonist N(6)-cyclopentyladenosine (CPA) elicited biphasic changes in the branchial and systemic resistances. While there was an initial decrease in the branchial resistance followed by an increase, the opposite was true for the systemic response. The resistance changes were significantly attenuated by aminophylline (a P(1)-receptor antagonist) and 8-cyclopentyltheophylline (CPT; an A(1)-receptor antagonist). In addition, adenosine induced an aminophylline-sensitive decrease in the arterial P(O2). The reduction was attenuated when pre-injection arterial P(O2) was low. Adenosine and CPA also caused a marked reduction in fh, with CPA being more potent. The bradycardia was blocked by aminophylline and CPT, demonstrating an involvement of A(1) receptors in this response.
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PMID:Cardiovascular responses to adenosine in the antarctic fish pagothenia borchgrevinki 1044 Oct 79

1. The effects of adenosine on synaptic transmission in magnocellular neurosecretory cells were investigated using whole-cell patch-clamp recordings in acute rat hypothalamic slices that included the supraoptic nucleus. 2. Adenosine reversibly reduced the amplitude of evoked inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents in a dose-dependent manner (IC50 approximately 10 microM for both types of current). 3. Depression of IPSCs and EPSCs by adenosine was reversed by the application of the A1 adenosine receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT; 10 microM). 4. When pairs of stimuli were given at short intervals, adenosine inhibitory action was always less effective on the second of the two responses than on the first, resulting in an increased paired-pulse facilitation and suggesting a presynaptic site of action. This observation was confirmed by analysis of spontaneous miniature synaptic currents whose frequency, but not amplitude or kinetics, was reversibly reduced by 100 microM adenosine. 5. CPT had no effect on synaptic responses evoked at a low frequency of stimulation (0.05-0.5 Hz), indicating the absence of tonic activation of A1 receptors under these recording conditions. However, CPT inhibited a time-dependent depression of both IPSCs and EPSCs induced during a 1 Hz train of stimuli. 6. Taken together, these results suggest that adenosine can be released within the supraoptic nucleus at a concentration sufficient to inhibit the release of GABA and glutamate via the activation of presynaptic A1 receptors. By its inhibitory feedback action on the major afferent inputs to oxytocin and vasopressin neurones, adenosine could optimally adjust electrical and secretory activities of hypothalamic magnocellular neurones.
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PMID:Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurones. 1054 29

Adenosine, an endogenous modulator of synaptic transmission, has been implicated in regulation of sleep and arousal. The effect of adenosine on neuronal excitability depends on its concentration in the extracellular space. The present study shows that the state of activity of laboratory rats determines the level of tonic inhibition by adenosine in hippocampal slices prepared from these animals. Thus, slices taken at the end of the active period showed significantly more inhibition by adenosine, as determined by the effects of the A1 receptor blocker 8-CPT, in comparison to slices taken in the inactive state. The results support the proposed role of adenosine in regulation of sleep and arousal and point to the importance of the time of day at which slices for electrophysiological experiments are prepared.
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PMID:Time of day determines modulation of synaptic transmission by adenosine in the rat hippocampal slices. 1071 26

We hypothesized that nitric oxide (NO) plays an important role in mediating the anti-adrenergic effect of adenosine on atrioventricular (AV) nodal conduction. In guinea-pig hearts instrumented for measurement of AV nodal conduction time (atrium-to-His bundle, A-H, interval), the NO synthase (NOS) inhibitor, l-NMMA (100 microm), reversibly inhibited 80% (P=0.009, n=6) of adenosine's anti-adrenergic action on the positive dromotropic effect of isoproterenol (0.01 microm). In parallel studies carried out in rabbit AV nodal myocytes, intracellular mechanisms whereby NO mediates the inhibitory effect of adenosine on isoproterenol-induced A-H interval shortening were studied. Adenosine (3 microm) inhibited isoproterenol-stimulated (0.1 microm) I(Ca,L)(beta -I(Ca,L)) by 46+/-6% (P<0.001, n=17). Consistent with isolated heart data, the NOS inhibitors, l -NMMA (100 microm) and L-NNA (500 microm) attenuated the effect of adenosine on beta -I(Ca,L)by 69+/-8% (P<0.001, n=16) and 69+/-7% (P<0.001, n=10), respectively. An inhibitor of NO-stimulated guanylyl cyclase LY83538 (40 microm) reduced the inhibitory effect of adenosine on beta -I(Ca,L)by 97+/-6% (P=0.004, n=15). Similarly, the non-specific inhibitor of cAMP-phosphodiesterases IBMX (50 microm) decreased the anti-adrenergic effect of adenosine by 60% (P=0.02, n=6), whereas the extracellular application of the non-hydrolyzeable cAMP analog 8-Br-cAMP (500 microm) prevented this action of adenosine. Activation of cGMP-dependent protein kinase (PKG) by CPT-cGMP (300 microm) diminished beta -I(Ca,L), but to a significantly smaller degree (16+/-4%, P=0.025, n=12) than that caused by adenosine. NO mediates the anti-adrenergic effect of adenosine on AV nodal conduction by a mechanism predominately involving activation of cGMP-dependent cAMP-phosphodiesterase and to a lesser extent activation of PKG.
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PMID:Antagonism of the positive dromotropic effect of isoproterenol by adenosine: role of nitric oxide, cGMP-dependent cAMP-phosphodiesterase and protein kinase G. 1096 24

Effects of adenosine and pGlu-Glu-ProNH(2) (FPP) on the function and in vitro penetration of boar spermatozoa were examined. First, the effects of dibutyryl cAMP or agonists and antagonists of adenosine receptors (inhibitory adenosine receptors, A1AdR; stimulatory adenosine receptors, A2AdR) on freshly ejaculated spermatozoa were determined by chlortetracycline fluorescence assessment. Capacitation of spermatozoa was stimulated when they were cultured in a medium with dibutyryl cAMP, adenosine, A2AdR agonist, and adenosine plus A1AdR antagonist (CPT). However, acrosome reaction was inhibited only by adenosine. A1AdR agonist did not affect intact spermatozoa. A2AdR antagonist (DMPX) neutralized all of the effects of adenosine. Second, interaction of adenosine and FPP was examined. Gln-FPP, a competitive inhibitor of FPP, and DMPX inhibited the effects of adenosine and FPP, and CPT neutralized the inhibitory effect of FPP on acrosome reaction. Last, the effects of adenosine, FPP, and caffeine on the rate of sperm penetration were examined using frozen-thawed spermatozoa. Adenosine, FPP, and caffeine significantly enhanced the rate of sperm penetration as compared with the case of no additions. Caffeine treatment resulted in a high rate of polyspermic fertilization. In contrast, adenosine and FPP treatments resulted in an increased proportion of normal fertilization in in vitro-matured oocytes. These results suggest that boar spermatozoa can be modulated by the adenylyl cyclase/cAMP pathway via A2AdR in intact cells to induce capacitation and A1AdR in capacitated cells to inhibit spontaneous acrosome loss and that FPP receptors interact with A2AdR in intact cells and with A1AdR in capacitated cells. Furthermore, adenosine and FPP seem to be useful in reducing the incidence of polyspermic penetration.
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PMID:Modulation of the function of boar spermatozoa via adenosine and fertilization promoting peptide receptors reduce the incidence of polyspermic penetration into porcine oocytes. 1099 40

The influence of adenosine receptor agonists and antagonists on amphetamine-induced stereotypy was examined in male Wistar rats. Adenosine A2 receptor agonists CGS 21680 (0.5-2 mg/kg ip) and a non-specific A2/A1 receptor agonist NECA (0.05-0.1 mg/kg ip) attenuated in a dose dependent manner amphetamine-induced stereotypy (2 mg/kg sc). CPA as specific agonist of adenosine A1 receptors counteracted this stereotypy, but only in a narrow range of doses (0.1-0.2 mg/kg ip). Adenosine A2A receptor antagonist, DMPX (3 and 6 mg/kg ip) potentiated stereotypy induced by either subthreshold dose of amphetamine 0.5 mg/kg or a high one 2 mg/kg. A non-selective adenosine receptor antagonist, caffeine (10 mg/kg ip) potentiated effect of low dose of amphetamine, but only in a dose of 20 mg/kg ip increased stereotypy induced by 2 mg/kg ip of amphetamine. A selective adenosine A1 receptor antagonist CPT (1 and 3 mg/kg ip) was ineffective in reversing amphetamine-induced stereotypy. These results confirm the existence of adenosine-dopamine interactions in the brain, and the suggestions that A2 adenosine receptor agonists may have antipsychotic properties.
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PMID:Influence of adenosine receptor agonists and antagonists on amphetamine-induced stereotypy in rats. 1133 36


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