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

1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It is unlikely therefore that cyclic GMP was causing excitation by chelating calcium.6. Applications of noradrenaline and cyclic AMP produced a reduction in the spontaneous discharge rate of most neurones tested.7. Phosphodiesterase inhibitors such as ICI 63,197 caused a potentiation of the noradrenaline responses of pyramidal tract neurones.8. 5'-adenosine monophosphate produced a powerful depression of all cells to which it was applied. This action was blocked by aminophylline, suggesting the effect was mediated through an adenosine receptor. Responses to cyclic AMP were usually not abolished, but were reduced by about 50% in amplitude.9. These results are consistent with the hypothesis that cyclic AMP may mediate some neuronal effects of noradrenaline and cyclic GMP may mediate some effects of acetylcholine. The results are also consistent with the suggestion that the two nucleotides may sometimes mediate opposite cellular responses to humoral stimuli.
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PMID:Microiontophoretic studies of the effects of cylic nucleotides on excitability of neurones in the rat cerebral cortex. 19 28

The actions of the highly selective A2 adenosine agonist, CGS 21680, in modulating kindled seizures and locomotor activity were examined. I.c.v. injections of CGS 21680 into the lateral cerebral ventricle in fully kindled rats were found to prolong the period of postictal EEG depression and reduce postictal spiking in a dose-dependent manner, while not affecting the behavioral seizure stage or afterdischarge duration. CGS 21680 injections also lead to a dose-related inhibition of locomotor activity in rats exposed to an open field apparatus compared to rats receiving control injections of saline. These observations implicate the involvement of the A2 adenosine receptor in postictal phenomena and the locomotor depressant actions of adenosine, but do not indicate a direct anticonvulsant activity following A2 activation.
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PMID:The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. 143 42

1. Endogenous adenosine, which is produced by enzymatic degradation of ATP released from synaptic vesicles, has been shown to be a potent inhibitor of acetylcholine release from motor nerve terminals. It has been proposed that this auto-inhibition mechanism might contribute significantly to tetanic stimulation-induced depression. 2. Levels of facilitation and depression during a 20 Hz stimulus train differ greatly in different terminals, but are strongly and non-linearly correlated with the terminal's release characteristics (the amount of transmitter released per unit terminal length, or 'release efficacy'). There is a weaker, approximately linear, correlation between depression and release efficacy at 2 Hz stimulation. 3. The effects of both endogenous and exogenously applied adenosine are also highly variable for different nerve terminals. We have shown that much of this variability can be attributed to the release efficacy of each terminal in the case of endogenous effects, and to the size of the nerve terminal in the case of exogenously applied adenosine receptor agonists. 4. When nerve terminals are pooled according to their individual release characteristics, endogenous adenosine can be shown to contribute significantly to stimulation-induced depression of release primarily in terminals that release enough transmitter to generate significant levels of adenosine, but do not release so much transmitter that depletion of releasable quanta is severe.
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PMID:Endogenous adenosine modulates stimulation-induced depression at the frog neuromuscular junction. 168 26

A limited occipital craniotomy was conducted on intact and decerebrate urethane-anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), a metabolically stable adenosine analog which exhibits mixed agonist properties for adenosine receptor subtypes, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co-existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 30-min test period. In the intact rat, microinjections of NECA produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. On the other hand, microinjections of NECA into this region of the NTS of the intact rat elicited complex, bi-directional cardiovascular responses, producing hypotension (at lower doses) and pressor responses (at higher doses) in addition to bradycardia (at lower doses). In an effort to examine the functional interactions between the NTS and forebrain structures involved in cardiorespiratory control, microinjections of NECA in the identical dose range were made into the same NTS sites of a separate group of urethane-anesthetized, spontaneously breathing rats in which reciprocal connections between forebrain areas and the brainstem had been disrupted by acute supracollicular decerebration. A simulating electrode, placed in the paraventricular nucleus of the hypothalamus (PVH), was used to confirm complete transection during the experiment and to ascertain the integrity of reciprocal connections between the brainstem and rostral brain regions involved in cardiorespiratory control. Although decerebration at the supracollicular level negligibly affected basal cardiorespiratory parameters, microinjections of NECA into the NTS revealed dramatic differences in the cardiovascular response patterns between intact and decerebrate rats. Whereas cardiovascular responses elicited by microinjections into the NTS were significantly affected by supracollicular decerebration, respiratory responses were highly similar for both intact and decerebrate animals. Indeed, repeated measures MANOVA indicated that there were no significant differences in the time-related or dose-related responses in the depression of respiration between decerebrate and intact rats following NECA microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The adenosine analog, 5'-N-ethylcarboxamidoadenosine, exerts mixed agonist action on cardiorespiratory parameters in the intact but not decerebrate rat following microinjections into the nucleus tractus solitarius. 227 53

A limited occipital craniotomy was conducted on urethane-anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), an adenosine analog, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co-existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 60 min test period. Microinjections of NECA, in the dose range of 0.35-350 pmol per rat, produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. In contrast, the effects of NECA microinjections on cardiovascular parameters in this region of the NTS were bidirectional and elicited considerably more complex responses during the test period. During the initial period (2-5 min) following injection, NECA elicited significant hypotension (at lower doses) and pressor responses (at higher doses) in addition to significant bradycardia (at lower doses) whereas by the end of the 60 min test period, almost all doses of NECA had resulted in hypertension and tachycardia. Multivariate analysis of variance (MANOVA) and correlation statistics indicated that the effects of NECA on blood pressure during the initial 2-5 min were dose-dependent and unlikely related to depression of respiratory frequency. A further examination of the data by MANOVA indicated that the pharmacological effects of NECA during the 60 min test period exhibited a highly significant and specific dose-dependent and time-related response pattern for the respiratory, but not the cardiovascular, parameters. Taken together, these manifold response patterns suggest that the respiratory effects of NECA may be mediated by different intrinsic mechanisms in the NTS than are the cardiovascular effects of NECA. At the end of the 60 min test period following the administration of NECA, the respiratory rate remained profoundly depressed. In view of previous studies showing that microinjections of cyclic AMP analogs, forskolin, isoproterenol and adenosine into the same NTS sites elicit a similar depression of respiration, the results with NECA in the present study further support the notion that cyclic AMP may serve as a second messenger in NTS respiratory control regions and these respiratory depressant effects may be mediated by a single adenosine receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiorespiratory function is altered by picomole injections of 5'-N-ethylcarboxamidoadenosine into the nucleus tractus solitarius of rats. 233 63

1. A series of related methylxanthines were studied for their effects on the kinetics of decay of end-plate currents (e.p.c.s) and miniature end-plate currents (m.e.p.c.s) at motor end-plates of the frog. 2. Isobutyl methylxanthine (IBMX, 50 microM-3 mM) produced a concentration-dependent depression of the peak e.p.c. and m.e.p.c. amplitude and a change in the kinetics of e.p.c. and m.e.p.c. decay from the normal single-exponential to a double-exponential function. Drug effects of this nature are generally attributed to open-channel blockade. 3. After wash-out of IBMX, the decay of the e.p.c. or m.e.p.c. was restored to a single-exponential function but with a significantly prolonged time constant. 4. Caffeine or theophylline derivatives (0.1-4 mM), during exposure to drug, produced effects similar to those observed after the application of IBMX; namely a prolongation of the time course of e.p.c.s and m.e.p.c.s without changing the single-exponential nature of the function. 5. Computer simulations were made of the m.e.p.c.s in IBMX. The effects of IBMX could be fitted to the sequential model of channel block only if the prolonged time constant observed upon wash-out was used for the rate constant of channel closure. Independent calculations of the rate constant of channel closure during IBMX application were in agreement with those measured during wash-out. 6. The theophylline derivative 8-phenyltheophylline, a selective adenosine receptor blocker with minimal effects on phosphodiesterase (PDE), increased the time constant of e.p.c. decay in a manner similar to theophylline and caffeine. Non-xanthine PDE inhibitors, either had no effect on m.e.p.c. decay (papaverine) or decreased the time constant of decay (RO 20-1724). It is thus unlikely that PDE inhibition is responsible for the post-junctional effects of IBMX. 7. IBMX (50 microM-2 mM) increased quantal ACh release in the virtual absence of extracellular calcium and also increased the efficacy of adenosine derivatives in inhibiting ACh release. Adenosine (10-100 microM) or 2-chloroadenosine (1-10 microM) had no effect on the time constant of e.p.c. decay nor did these adenosine receptor agonists alter the post-junctional actions of IBMX. The effects of IBMX on end-plate channel kinetics are thus not due to the blockade of adenosine receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Independent control of channel closure and block of open channels by methylxanthines at acetylcholine receptors in frog. 245 Sep 93

The behavioral stimulant effects of xanthines, such as caffeine and theophylline, appear to involve blockade of central adenosine receptors. However, 3-isobutyl-1-methylxanthine (IBMX), a potent phosphodiesterase (PDE) inhibitor, produces behavioral depression. The effects of caffeine analogs on open field behavior of mice and potencies as antagonists of adenosine receptors and as inhibitors of three classes of brain PDE have been compared. 1,7-Dimethyl-3-propargylxanthine, 1,3,7-tripropargylxanthine, and 3,7-dimethyl-1-propargylxanthine, which have high affinity for adenosine receptors and weaker activity as PDE inhibitors, all increase behavioral activity. In contrast, 1,3,7-tripropylxanthine, a more potent inhibitor of the brain calcium-independent (Ca-indep) PDEs than 1,3,7-tripropargylxanthine, produces behavioral depression, even though both analogues are potent adenosine receptor antagonists. 7-Benzyl-IBMX, an active receptor antagonist and selective inhibitor of a brain calcium-dependent (Ca-dep) PDE, produces a slight behavioral activation. Xanthines that are potent adenosine receptor antagonists and relatively weak inhibitors of the Ca-indep PDEs reverse the depressant effects of N6-cyclohexyladenosine, while xanthines, such as 1,3,7-tripropylxanthine, that are potent inhibitors of the Ca-indep PDEs, do not. The results suggest that the behavioral effects of xanthines may be determined primarily by relative activity as adenosine receptor antagonists and as inhibitors of brain Ca-indep PDEs.
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PMID:Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors. 245 42

There is only limited information available on the prejunctional regulation of acetylcholine (ACh) release from cholinergic nerves in human airway smooth muscle. Stimulation of cholinergic nerves in fresh postmortem tracheal muscle strips with electrical field stimulation (EFS) causes reproducible contractions. We have studied the effect on contractile responses of: 1) The alpha 2-adrenoceptor agonist effect of noradrenaline (NA, 0.1-30 microM) and clonidine (10 nM-30 microM), in the presence of 1 microM propranolol and prazosin +/- idazoxan (0.1 microM); 2) The beta-adrenoceptor agonist effect of fenoterol (FEN) and isoprenaline (ISO, 1 nM-30 microM) +/- ICI 118,551 (10 nM), comparing EFS responses to comparable responses to exogenous ACh; 3) The A1 and A2 adenosine receptor agonists effects of L-PIA and NECA (1 nM-10 microM). NA caused a concentration-dependent depression of the cholinergic frequency-response curve. However responses at 5 Hz were not modified by the addition of idazoxan. Similarly clonidine did not reduce contractile responses. The concentrations of isoprenaline (56 nM) and fenoterol (165 nM) required to inhibit EFS (5 Hz) by 50% (IC50) were significantly less than those required to inhibit closely matched ACh responses to a comparable degree (ISO = 117 and FEN = 304 nM), and the maximum inhibition of EFS was greater. Following isoprenaline and the beta 2-antagonist ICI 118,551 the IC50's for EFS and ACh were not different. NECA and PIA had no effect on cholinergic EFS. We conclude that a prejunctional beta 2 receptor may be present on cholinergic nerves in post-mortem tracheal smooth muscle but no evidence for alpha 2-adrenoceptor or adenosine-receptor regulation was obtained.
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PMID:Effects of adrenergic agonists and adenosine on cholinergic neurotransmission in human tracheal smooth muscle. 256 55

1. Iontophoretic application of the veterinary tranquilizer xylazine suppressed the spontaneous firing of 134/137 neurons tested, an effect not antagonized by adenosine receptor and alpha-adrenergic receptor blocking agents. 2. Depressions in neuronal activity evoked by norepinephrine, gamma-aminobutyric acid or adenosine failed to be potentiated by xylazine. 3. However, the excitatory effects of acetylcholine and glutamate were both inhibited by xylazine. 4. Thus, the depressant effect of locally applied xylazine may involve a decrease in the excitability of the neuronal membrane.
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PMID:Xylazine-evoked depression of rat cerebral cortical neurons: a pharmacological study. 256 68

Previous studies suggest that high levels of adenosine may enhance histamine release and contribute to atrioventricular (AV) nodal conduction arrhythmias during anaphylaxis of isolated guinea pig hearts. To determine whether elevations in endogenous adenosine evoked by hypoxic conditions have similar effects, isolated hearts of guinea pigs passively sensitized by intracardiac injection were perfused with solutions equilibrated with 95% O2 (normoxia) or 30% O2 (hypoxia). When compared with normoxia, hypoxia before antigen challenge increased adenosine release, decreased vascular resistance, and prolonged P-R intervals, whereas hypoxia during anaphylaxis potentiated the increase in adenosine release, attenuated the increases in vascular resistance and atrial rate, and increased the occurrence of conduction arrhythmias without altering the antigen-induced release of either histamine or thromboxane. Addition of the adenosine receptor antagonist 8-(4-sulfophenyl)theophylline (SP-T) to the hypoxic perfusate significantly decreased antigen-induced release of histamine and thromboxane. These data indicate that 1) hypoxia-induced depression of antigen-induced mediator release may be counteracted by the stimulatory effect of the increased adenosine induced by hypoxia, and 2) under hypoxic conditions, adenosine's negative dromotropic, chronotropic, and vasodilatory effects may influence the anaphylactic reaction.
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PMID:Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts. 258 93


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