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

Iontophoretic application of carbachol caused excitation of CA1 neurones and decreased the amplitude of antidromic CA1 population spikes recorded extracellularly. Adenosine, adenosine triphosphate (ATP) and the purine analogues N-ethylcarboxamide adenosine (NECA) and R- and S-phenylisopropyladenosine (PIA) reduced the effects of carbachol on single cell firing and on the population spike. Responses to excitatory amino acids were unaffected by adenosine except for a small depression of kainate and N-methyl-D-aspartate responses at high concentrations. The rank order of potency for the purine reduction of carbachol responses was R-PIA = S-PIA = NECA much greater than adenosine greater than ATP. The actions of purines and purine analogues were antagonized by 8-phenyltheophylline (8-PT) and other xanthine antagonists. Application of 8-PT and other xanthines without prior exposure to purines frequently resulted in marked potentiation of carbachol responses. Thus in the hippocampus, responses to the cholinomimetic carbachol are markedly and selectively reduced by purines acting at the P1 purine receptor type and it appears that endogenous levels of adenosine limit the effects of cholinergic agents.
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PMID:Purine modulation of cholinomimetic responses in the rat hippocampal slice. 320 90

Adenosine is formed from adenosine triphosphate within the ischaemic cells from where it is released into the coronary circulation. Adenosine exhibits several cardiovascular effects which tend to protect the ischaemic myocardium. Based on the observation that in healthy volunteers the intravenous infusion of adenosine produces angina-like chest pain, it has been recently proposed that another cardioprotective action of this substance could be provocation of angina. If this is the case adenosine should not produce chest pain in patients with silent ischaemia. To test this hypothesis we infused this substance intravenously at increasing doses of 50, 100, 150, 200, 250 and 300 micrograms kg-1 min-1 in eight patients with silent ischaemia (group A). All of them developed ST depression (1.8 +/- 0.2 mm) during exercise testing and seven also during adenosine infusion (1.1 +/- 0.8 mm). However, none of the patients had chest pain during exercise while seven had chest pain during adenosine. We then infused adenosine in eight other patients (Group B) who had painful ischaemia and an exercise tolerance similar to that of Group A patients (time to 1 mm ST depression 8.6 +/- 2.7 min and 8.4 +/- 3 min, respectively, P = NS). Adenosine induced chest pain in all Group B patients. The time to pain onset during adenosine was similar in the two groups (9.3 +/- 2.3 min in Group B and 12.4 +/- 4.9 min in Group A).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine-induced chest pain in patients with silent and painful myocardial ischaemia: another clue to the importance of generalized defective perception of painful stimuli as a cause of silent ischaemia. 324 54

An open-chest preparation was carried out in 14 pentobarbitone anaesthetized dogs in order to evaluate the myocardial effects of controlled hypotension induced by adenosine in the presence of a severe coronary stenosis that caused ischaemia of the left anterior ventricular wall. Myocardial performance, blood flow and metabolism were studied before and during a 78 +/- 3% reduction of flow in the left anterior descending coronary artery (LAD) and during adenosine-induced hypotension (approximately 40% reduction of the mean arterial pressure) in the presence of the LAD stenosis. The LAD stenosis decreased the myocardial lactate uptake (P less than 0.01), increased ST-T segment depression (P less than 0.05) of the left ventricular subendocardial ECG, and reduced cardiac output by 10% (P less than 0.05). In the presence of stenosis, the mean arterial pressure was reduced by adenosine from 10.4 +/- 0.6 kPa to 6.3 +/- 0.2 kPa for 15 min. Heart rate decreased by 22% (P less than 0.01). There was no change in cardiac output during hypotension, while the rate-pressure product decreased by 47% (P less than 0.01) and myocardial oxygen consumption decreased by 30 +/- 7%. Adenosine increased the coronary sinus blood flow by 52% (P less than 0.01), while the LAD flow distal to the stenosis was not significantly reduced. Myocardial lactate uptake was not further reduced and subendocardial ECG signs of ischaemia were not aggravated by the hypotension. In conclusion, adenosine-induced hypotension did not aggravate the subendocardial ECG signs of acute poststenotic myocardial ischaemia. Nor did myocardial lactate determinations indicate aggravation of myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of adenosine-induced hypotension on the canine myocardium rendered acutely ischaemic by artificial stenosis. 339 84

Adenosine modulates a variety of physiological functions through interaction with A1 and A2 adenosine receptors, where agonists mediate inhibition and stimulation, respectively, of adenylate cyclase. In the cardiovascular system, A2 receptors mediate vasodilation and reduction in blood pressure, while A1 receptors mediate cardiac depression. The involvement of adenylate cyclase in these responses remains unresolved. Adenosine analogs in particular the N6-substituted compounds are more potent at A1 receptors than at A2 receptors. The subregion of the adenosine receptor that interacts with the N6-substituent is different for A1 and A2 receptors, particularly with respect to phenyl interactions, bulk tolerance and stereoselectivity. A series of para-substituted N6-phenyladenosines have been synthesized based on a "functionalized congener" approach in which a chemically reactive group, such as an amine or carboxylic acid, is introduced at the terminus of a chain. From the "functionalized congener" are synthesized a variety of conjugates each containing a common pharmacophore. Certain of the adenosine conjugates are highly selective for A1 receptors. Xanthines are classical antagonists for adenosine receptors for many of their pharmacological actions may be due to blockade of adenosine receptors. Caffeine and theophylline are virtually non-selective for A2 and A2 receptors. Replacement of the methyl groups of theophylline with n-propyl or larger alkyl groups yields xanthines with selectivity for A1 receptors, particularly when combined with an 8-phenyl moiety. Most 1,3-dialkyl-8-phenyl xanthines are very insoluble, but incorporation of polar aryl substituents, such as sulfo or carboxy to increase solubility, results in marked reduction in potency and selectivity. A new series of more hydrophilic 1,3-dipropyl-8-phenylxanthines has been synthesized using the "functionalized congener" approach. Certain conjugates of 8-[4-(carboxymethyloxy)phenyl 1]1,3-dipropylxanthine display A1 selectivity in biochemical and cardiovascular models. Certain analogs of caffeine in which the methyl group at the 1- or 7-position is replaced with a propargyl or propyl group display selectivity for A2 receptors. The profile of a series of adenosine analogs or of xanthine antagonists can be used to define the nature of adenosine receptors.
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PMID:Adenosine receptors: development of selective agonists and antagonists. 358 7

We administered intravenous adenosine to 11 neonatal rabbits. Adenosine depressed respiration in 10 of 11 rabbits. For the group as a whole the adenosine-induced respiratory depression was highly significant (p less than 0.001). After aminophylline administration to the same animals the respiratory effect of intravenous adenosine was abolished in 3 animals. In 7 animals the effect of adenosine was reversed and respiratory stimulation was observed. After aminophylline adenosine produced a significant (p less than 0.001) increase in respiration in the group studied. The alteration of responses to intravenous adenosine by aminophylline in neonatal rabbits is similar to the effect of aminophylline on respiratory responses to hypoxia in neonates. Such an effect of aminophylline and other methylxanthines on adenosine actions, possibly central in site may explain their beneficial effect in the treatment of apnoea in the human neonate.
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PMID:Effect of aminophylline on the respiratory depressant action of intravenous adenosine in neonatal rabbits. 379 10

The cardiovascular effects of adenosine-induced hypotension were studied in 47 patients undergoing intracranial vascular surgery under neurolept anesthesia. Adenosine infusion (214 +/- 18 micrograms X kg-1 X min-1) decreased mean arterial pressure (MAP) by 42 +/- 1% from 80 +/- 1 to 46 +/- 1 mm Hg for an average of 29 +/- 5 min of hypotension. Hypotension was associated with a minor increase in heart rate (13 +/- 2%) and with prolongation of the PR interval (9 +/- 2%). ST-T depression did not occur except in one patient with a previous history of myocardial infarction. The adenosine-induced increase in cardiac index (42 +/- 9%, n = 7) was associated with a 63 +/- 10% decrease in systemic vascular resistance index (n = 7) while the pulmonary capillary wedge pressure remained unchanged. Adenosine metabolism was limited and there was no accumulation of the end metabolite, uric acid. Serum creatinine levels were normal in all patients postoperatively. We conclude that adenosine rapidly induces a stable and easily controlled hypotension in man without tachyphylaxis or rebound hypertension. There were no signs of renal or myocardial dysfunction except for dysrhythmias that occurred in two patients with a history of myocardial infarction.
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PMID:Clinical experience with adenosine for controlled hypotension during cerebral aneurysm surgery. 382 65

The action of adenosine on the electrically induced mechanical response of circular muscle in isolated guinea-pig ileum has been investigated. Electrical stimulation (0.1 Hz) elicited the twitch response, which was completely abolished by tetrodotoxin (0.2 microM), morphine (1 microM) and atropine (0.1 microM). Adenosine (0.1-100 microM) markedly depressed the twitch response in a concentration-dependent manner, and the concentration-depression curve for adenosine was significantly shifted to the right in the presence of theophylline (30 microM). On the other hand, the contractile responses induced by acetylcholine (1-300 microM) were not effected by adenosine at all. The present investigation suggests that the twitch response is mediated through acetylcholine released from the intramural cholinergic nerves supplying the circular muscle of guinea-pig ileum, and adenosine has an inhibitory effect on the cholinergic transmission, probably via P1-purinoceptors.
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PMID:Effects of adenosine on contractile response of circular muscle in electrically stimulated guinea-pig ileum. 406 77

The possibilities of participation of adenosine in the peristaltic reflex of guinea pig ileum was studied pharmacologically and histologically. Adenosine apparently depressed the peristaltic activity induced by elevation of intraluminal pressure from zero to 1-8 cm H2O, and the extent of the depression somewhat decreased in proportion to the elevation in intraluminal pressure. Also, dipyridamole depressed the peristaltic activity by itself; however, the extent of the depression significantly increased in proportion to the elevation in intraluminal pressure. On the other hand, in the presence of dipyridamole, the elevation of the intraluminal pressure from zero to 1-8 cm H2O elicited an 3H-output increase from 3H-adenosine preloaded guinea pig isolated ileum, with the effect being more pronounced as the pressure was increased. In contrast, the peristaltic activity was more pronounced at lower pressurization. Atropine greatly depressed the peristaltic response but did not affect 3H-output induced by 4 cm H2O pressurization. Tetrodotoxin depressed both markedly. Fluorescence histochemical localization of quinacrine, which binds to adenosin triphosphate (ATP), revealed dense nerve cell bodies and fine interconnecting strands in the ileal myenteric plexus of Auerbach. Also, in microradioautographs of ileal longitudinal muscle incubated with 3H-adenosine, the concentration of developed silver grains was localized in the ganglion cells and in the musculature as varicose fibre. From these results, evidence is provided that the peristalsis of guinea pig ileum may be physiologically modulated by endogenous adenosine, which may be released from neuronal elements of the myenteric plexus in response to the applied intraluminal pressure.
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PMID:Possibilities for adenosine modulation of peristaltic reflex in guinea pig isolated ileum. 409 42

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

1. Adenosine and its analogs depress the firing of neurons in various brain regions. The primary mode of action of adenosine in exerting this effect appears to be the depression of transmitter release from presynaptic nerve terminals. This is a result of reduced calcium mobilization. 2. Adenosine uptake inhibitors and deaminase inhibitors depress the firing of central neurons. Adenosine antagonists, caffeine and theophylline, excite central neurons. Adenosine is therefore likely to be released in sufficient quantities to exert an ongoing modulation of synaptic transmission in the intact brain. 3. A number of groups of centrally active drugs inhibit adenosine uptake by brain synaptosomal preparations. These include the benzodiazepines, phenothiazines, various other sedatives and hypnotics, tricyclic antidepressants, non-steroidal anti-inflammatory analgesics, some steroids, diphenylhydantoin, puromycin and toyocamycin. 4. It is proposed that many agents with anxiolytic, sedative, analgesic or anti-convulsant actions may achieve their effects by inhibiting adenosine uptake and thus potentiating extracellular adenosine levels. 5. Morphine also elevates extracellular adenosine levels but achieves this by enhancing adenosine release.
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PMID:The effect of various centrally active drugs on adenosine uptake by the central nervous system. 612 37


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