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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In slices of rat hippocampus, adenosine and several adenosine derivatives depressed evoked neuronal responses to afferent stimulation. The nanomolar potency of adenosine derivatives and their relative effectiveness indicate that the depression of evoked potentials is mediated via an A1-adenosine receptor. A remarkable similarity was found between the relative potencies of nucleoside derivatives with respect to their electrophysiological effects and to their inhibition of high affinity [3H] cyclohexyladenosine ([3H]CHA) binding to rat brain membranes. We conclude that the [3H] CHA binding site in rat brain membranes represents a physiological receptor of the A1-type.
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PMID:An A1-adenosine receptor, characterized by [3H] cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampal slice preparation. 628 93

In this study, extracellular recordings were made from wide dynamic range (WDR) neurons in lumbar segments of the spinal cord in rats transsected at the first lumbar segment. The nociceptive discharges of WDR neurons were depressed by weak electro-acupuncture applied to "Yanglingquan"-"Xuanzhong" points. The depression was blocked by i.v. administration of adenosine receptor antagonists, theophylline and caffeine. The observations indicate that depression of the nociceptive response of the WDR neurons induced by weak EA may be mediated by adenosine within the spinal cord.
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PMID:[Role of adenosine in weak electro-acupuncture-induced depression of nociceptive response of spinal dorsal horn neurons in rats]. 775 Jan 77

The biphasic nature of the ventilatory response to sustained hypoxia (< 1 h) is thought to occur as a result of combined effects of stimulation and depression with hypoxia. If the depressant effect of hypoxia on ventilation occurs later than the stimulatory effect, the magnitude of the ventilatory response to progressive hypoxia may be different according to the time required for a given fall in PaO2 during the test. In this study, we measured, in 10 healthy adult volunteers, ventilatory responses to isocapnic progressive hypoxia (HVR) using three different protocols (4 min, 6 min, and 15 min for SaO2 to decrease from the baseline to 80%) with or without pretreatment using theophylline (300 mg twice a day), an adenosine receptor antagonist, in a 2-d, single-blind crossover design. The slope values of HVR with the placebo were 0.31 +/- 0.04 (SE) (L/min/% fall of SaO2) in the 4-min protocol, 0.26 +/- 0.04 in the 6-min protocol, and 0.18 +/- 0.04 in the 15-min protocol. The HVR for the 15-min protocol was significantly lower than that for the 4-min or 6-min protocol. The HVR with theophylline was 0.46 +/- 0.08 for the 4-min protocol, 0.54 +/- 0.09 for the 6-min protocol, and 0.66 +/- 0.11 for the 15-min protocol, among which there were no significant differences. The dependency of HVR on the rate of change in PaO2, that was seen with a placebo run, disappeared after pretreatment with theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dependency on the rate of change in PaO2 of the ventilatory response to progressive hypoxia. 776 25

Rabbit atria were isolated with the extrinsic right sympathetic and vagus nerves attached and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. Sympathetic nerve stimulation (SNS, 2 Hz, 3 min) carried out together with vagus nerve stimulation (VNS, 2 Hz, 3 min), but each SNS pulse preceding a vagal one by 19 ms, caused a facilitation of acetylcholine overflow of about 60% versus independent controls in the absence of SNS. Antagonists of putative neurotransmitters were tested to find out the prejunctional mediator involved in the facilitation. The facilitation was not significantly reduced by prazosin, rauwolscine, idazoxan, or propranolol, excluding mediation by alpha- or beta-adrenoceptors. However, guanethidine abolished evoked noradrenaline release and facilitation, suggesting that it is due to a compound co-released with noradrenaline from postganglionic noradrenergic nerves. Pretreatment of rabbits with reserpine which reduced noradrenaline content of atria and SNS evoked overflow by 94% did not affect the facilitation of acetylcholine release which, due to the cardiostimulatory action of SNS being absent, resulted in enhanced depression of atrial force. We conclude that the facilitation is due to release of a reserpine-resistant co-transmitter from sympathetic nerves. Possible mediation of the facilitation by ATP through P2X- or P2Y-purinoceptors was excluded by ineffectiveness of alpha, beta-methylene ATP-preperfusion, of suramin and cibacron blue, respectively. However, the selective A2 adenosine receptor antagonist CP 66,713 reduced the facilitation by 25% whereas DPCPX (A1-selective) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Co-transmitter mediated facilitation by sympathetic nerve stimulation of evoked acetylcholine release from the rabbit perfused atria preparation. 777 98

We previously reported that adenosine has significant depressor effects in the nucleus tractus solitarii and area postrema of the rat. The purpose of this study was to determine whether the spontaneously hypertensive rat (SHR) has abnormalities in medullary sensitivity to adenosine. Male SHR and Wistar-Kyoto (WKY) rats (aged 12 to 15 weeks) were anesthetized with urethane, and blood pressure was monitored intraarterially. Stereotaxic microinjection (60 nL) of adenosine was made into the nucleus tractus solitarii and the area postrema and was confirmed histologically. Dose-related decreases in mean blood pressure and heart rate occurred in both strains tested, and this effect was completely abolished by 1,3-dipropyl- 8-p-sulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist. However, there were significant differences between SHR and WKY rats in the magnitude of blood pressure and heart rate depression. A similar pattern of response was found in the area postrema. Thus, adenosine is a potent depressor agent in the nucleus tractus solitarii and area postrema of rats, and adenosine has significantly fewer depressor effects in SHR. These data suggest that alterations in purinergic mechanisms of central cardiovascular control exist in the SHR model.
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PMID:Attenuated cardiovascular response to adenosine in the brain stem nuclei of spontaneously hypertensive rats. 784 79

1. Previous work has suggested that presynaptic effects of adenosine may be dependent on divalent cations. The present study was undertaken to determine whether a similar requirement existed at postsynaptic sites. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum or antidromic stimulation of the alveus. In antidromic stimulation experiments, CaCl2 was omitted (calcium-free medium) or reduced to 0.24 mM (low calcium medium) and in some experiments MgSO4 was increased to 2 mM. Kynurenic acid at concentrations of 1 and 5 mM in calcium-free medium and 1 mM in low calcium medium had no effect on secondary spike size. 3. Adenosine and baclofen induced a concentration-dependent reduction in the amplitude of orthodromic potentials with maximum effects at 20 and 5 microM respectively. 4. In nominally calcium-free medium, bursts of multiple population spikes were obtained in response to antidromic stimulation. Adenosine had little effect in reducing the secondary spike amplitude. At high concentration (2 mM) an initial depression was seen which declined within 3-5 min. 5. Sensitivity to adenosine was restored in low calcium medium or by raising magnesium. Although raising the divalent cation concentration increased the inhibitory effect of adenosine, desensitization was still seen. 6. 2-Chloroadenosine (100-500 microM) and R-PIA (50 microM), which are not substrates for either the nucleoside transporters or adenosine deaminase, were inactive in the absence of calcium. S-(2-hydroxy-5 nitrobenzyl)-6-thioinosine, an adenosine uptake blocker, at a concentration 100 MicroM had no effect on secondary potential size and did not restore adenosine sensitivity in calcium-free medium.7. Thapsigargin, which discharges intracellular calcium stores, had no significant effect at 1 MicroM on the bursts of action potentials and did not change the effect of 0.5 mM adenosine in calcium-free medium.8. Unlike adenosine, baclofen concentration-dependently reduced the secondary spike size in calcium free medium and no sign of recovery was observed during maintained superfusion for up to 45 min. No cross-desensitization was seen between baclofen and adenosine.9. Applications of adenosine locally by pressure to neuronal somata or dendrites still resulted in desensitized responses in calcium-free medium.10. It is concluded that the postsynaptic sensitivity to adenosine is dependent on the concentration of divalent cations in the extracellular space implying an effect of cations on adenosine receptor activation or transduction processes.
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PMID:The effect of calcium removal on the suppression by adenosine of epileptiform activity in the hippocampus: demonstration of desensitization. 803 57

The exceptional ability of the turtle brain to survive prolonged anoxia makes it a unique model for studying anoxic survival mechanisms. We have used epi-illumination microscopy to record blood flow rate in venules on the cortical surface of turtles (Trachemys scripta). During anoxia, blood flow rate increased 1.7 times after 45-75 min, whereupon it fell back, reaching preanoxic values after 115 min of anoxia. Topical superfusion with adenosine (50 microM) during normoxia caused a 3.8-fold increase in flow rate. Superfusing the brain with the adenosine receptor blocker aminophylline (250 microM) totally inhibited the effects of both adenosine and anoxia, while aminophylline had no effect on normoxic flow rate. None of the treatments affected systemic blood pressure. These results indicate an initial adenosine-mediated increase in cerebral blood flow rate during anoxia, probably representing an emergency response before deep metabolic depression sets in.
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PMID:Time course of anoxia-induced increase in cerebral blood flow rate in turtles: evidence for a role of adenosine. 806 83

1. The hypothesis that ATP released by presynaptic stimulation is hydrolysed to adenosine and mediates prejunctional neuromuscular depression was tested at vertebrate neuromuscular junctions. Electrophysiological recordings of evoked acetylcholine (ACh) release and perineural ionic currents at motor nerve endings were made using the frog cutaneous pectoris nerve-muscle preparation. Either tubocurarine or alpha-bungarotoxin was used to block muscle contractions. 2. Either alpha,beta-methylene ADP (which inhibits ecto-5'nucleotidases and thus prevents the degradation of ATP to adenosine) or selective adenosine receptor antagonists (8-cyclo-pentyl alkyl xanthines) prevented the inhibitory effects of exogenous ATP on ACh release in response to low-frequency nerve stimulation. These results confirm earlier findings that ATP must be hydrolysed to adenosine to inhibit ACh release. 3. The presence of alpha,beta-methylene ADP completely prevented neuromuscular depression in response to repetitive high-frequency nerve stimulation (0.5-1 Hz). alpha,beta-Methylene ADP had no effect on ACh secretion under conditions where ACh release is well maintained (low-frequency stimulation, 0.05 Hz). 4. Selective adenosine receptor antagonists completely eliminated neuromuscular depression produced by repetitive high-frequency nerve stimulation (1.0 Hz) but had no effect on ACh release at low frequencies of stimulation (0.05 Hz). 5. Exogenous adenosine deaminase (5 i.u. ml-1), which degrades adenosine to its inactive nucleoside inosine, also eliminated neuromuscular depression but had no significant effect on ACh release at frequencies of nerve stimulation too low to produce prejunctional depression. 6. During maximal neuromuscular depression, the effects of exogenous adenosine or 2-chloroadenosine, an adenosine agonist, were occluded. 7. The calcium-sensitive component of perineurial recordings of motor nerve terminal currents did not change during depression or during application of adenosine receptor antagonists and adenosine deaminase, suggesting that neuromuscular depression in this species was not associated with changes in presynaptic Ca2+ currents. 8. These results suggest that, under the conditions of these experiments, endogenous ATP, after hydrolysis to adenosine, causes prejunctional neuromuscular depression. This inhibitory effect of endogenous adenosine occurs at a site distal to the locus of Ca2+ entry in the frog.
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PMID:ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings. 807 78

Adult male mice were stereotaxically implanted with permanent indwelling guide cannulae for bilateral injections into the nucleus accumbens (ACB). The effects on spontaneous locomotor activity of selective agonists for adenosine receptor subtypes were examined following bilateral injections into the ACB. Intra-ACB injections of CGS 21680, a potent and selective agonist at striatal adenosine A2a receptors, elicited pronounced, dose-related reductions in locomotor activity whereas similar bilateral dosages of CPA, a selective agonist at adenosine A1 receptors, did not significantly affect locomotor activity. The pronounced locomotor depression elicited by intra-ACB injections of CGS 21680 were completely blocked by I.P. pretreatment with DMPX, an adenosine receptor antagonist exhibiting selectivity for striatal A2 receptors, at a dosage which alone had no significant effect on locomotor activity. Adenosine A2a receptors in the nucleus accumbens may selectively modulate dopamine-mediated mesolimbic behavioral circuits involved in spontaneous locomotion.
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PMID:Role of adenosine A2a receptors in the nucleus accumbens. 807 88

The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein. Among the mechanisms that could contribute to the depression of neurotransmitter release is reduced entry of calcium through channels located in the presynaptic terminal. In the present study, we have examined the effects of adenosine on high-voltage-activated (HVA) calcium currents in motoneurons, the presynaptic cells of the neuromuscular junction. The motoneurons were isolated from embryonic mice, placed in primary tissue culture for 16 hr, and analyzed by means of the whole-cell patch-clamp technique. Adenosine (40 microM) reduced both transient and sustained components of HVA calcium current. This effect was blocked by the A1 antagonist 8-cyclopentyltheophylline (CPT; 100 nM) and was mimicked by the A1 agonist N6-cyclohexyladenosine (CHA; 50 nM to 10 microM) but not by the A2a agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine (CGS-21680; 1 micron). Pretreatment with pertussis toxin (200 ng/ml, > 16 hr) abolished the depression of HVA calcium current by adenosine receptor activation. Brief (3 min) exposure of the cells to 10 microM omega-conotoxin GVIA irreversibly blocked a part of the HVA current, which can therefore be attributed to N-type channels; the remaining current was unaffected by adenosine receptor activation. Hence, it appears that adenosine decreases only the N-current portion of HVA current and that this inhibition occurs via an A1 receptor linked to a pertussis toxin-sensitive G protein. Other investigators have shown that N-type channels do not play a primary role in eliciting transmitter release at the mammalian neuromuscular junction. Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels.
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PMID:Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. 820 77


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