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J A Ribeiro

Publications and source records attributed to J A Ribeiro.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus.

The A2 adenosine receptor agonist, CGS 21680 in nanomolar concentrations, reversibly increased in a concentration-dependent manner the amplitude of orthodromically-evoked population spikes recorded from the CA1 pyramidal cell layer of rat hippocampal slices. The adenosine receptor antagonist, 3,7-dimethyl-l-propargylxanthine (DMPX, 10 microM), which has selectivity for A2 adenosine receptors, prevented this excitatory effect of CGS 21680. These results suggest that A2 adenosine receptors are present in the rat hippocampus and that activation of these receptors enhance hippocampal excitability.

Adenosine↗
PubMed1992

Effects of forskolin, dibutyryl cyclic AMP, and 5'-N-ethylcarboxamide adenosine on 22Na uptake by rat brain synaptosomes stimulated by veratridine.

The effects of forskolin, dibutyryl cyclic AMP, and 5'-N-ethylcarboxamide adenosine on specific 22Na uptake by synaptosomes stimulated by veratridine were investigated. All substances inhibited 22Na uptake, with forskolin more potent than 5'-N-ethylcarboxamide and this latter one more potent than dibutyryl cyclic AMP. In the absence of preincubation with forskolin, this substance caused little or no effect on 22Na uptake by synaptosomes. In the presence of the adenosine antagonist dipropylsulfophenylxanthine, the inhibitory effect of 5'-N-ethylcarboxamide adenosine on 22Na uptake was consistently antagonized. The results were interpreted as forskolin and 5'-N-ethylcarboxamide adenosine increasing cyclic AMP accumulation, and dibutyryl cyclic AMP mimicking it, and by these mechanisms decreasing sodium uptake through the sodium channels.

Adenosine↗
PubMed1992

Ecto-5'-nucleotidase is associated with cholinergic nerve terminals in the hippocampus but not in the cerebral cortex of the rat.

The extracellular catabolism of exogenously added AMP was studied in immunopurified cholinergic nerve terminals and in slices of the hippocampus and cerebral cortex of the rat. AMP (10 microM) was catabolized into adenosine and inosine in hippocampal cholinergic nerve terminals and in hippocampal slices, as well as in cortical slices. IMP formation from extracellular AMP was not detected. alpha, beta-Methylene ADP (100 microM) inhibited almost completely the extracellular catabolism of AMP in these preparations. The relative rate of catabolism of AMP was greater in hippocampal slices than in cortical slices. AMP was virtually not catabolized when added to immunopurified cortical cholinergic nerve terminals, although ATP could be catabolized extracellularly under identical conditions. The comparison of the relative rates of catabolism of exogenously added AMP, calculated from the amount of AMP catabolized after 5 min, in hippocampal cholinergic nerve terminals and in hippocampal slices revealed a nearly 50-fold enrichment in the specific activity of ecto-5'-nucleotidase upon immunopurification of the cholinergic nerve terminals from the hippocampus. The results suggest that there is a regional variation in the subcellular distribution of ecto-5'-nucleotidase activity in the rat brain, the ecto-5'-nucleotidase in the hippocampus being closely associated with the cholinergic nerve terminals, whereas in the cerebral cortex ecto-5'-nucleotidase activity seems to be located preferentially outside the cholinergic nerve terminals.

5'-Nucleotidase↗
PubMed1991

Adenosine and the bradycardiac response to vagus nerve stimulation in rats.

The effects of intracardiac infusions of adenosine on the changes in heart rate (HR), electrocardiogram (ECG) and arterial blood pressure (BP) induced by both vagal stimulation and exogenous acetylcholine (ACh) were studied in anesthetized rats. Adenosine inhibited the bradycardia induced by vagal nerve stimulation, an effect antagonized by theophylline, decreased the elongation caused by vagal stimulation of the R-R intervals of the ECG, and caused a small but consistent decrease in the hypotensive effect of vagus nerve stimulation. At the dose that reduced the bradycardiac responses to vagal stimulation, adenosine enhanced the bradycardiac effect of exogenous ACh, increased R-R intervals and the number of P waves not followed by the ECG and had little or no effect on the inhibition induced by ACh on BP. The effects of adenosine on the bradycardiac responses to vagal nerve stimulation or to ACh administration were similar in both non-reserpinized and reserpinized animals. These results suggest that exogenous adenosine can modify the vagal influences on the heart by exerting pre-junctional inhibition of the vagus nerve and post-junctional enhancement of the ACh actions, and that the adrenergic system does not contribute to these effects of adenosine.

Acetylcholine↗
PubMed1991

Effect of adenosine on 45Ca2+ uptake by electrically stimulated rat brain synaptosomes.

The effect of adenosine on 45Ca2+ uptake by rat brain synaptosomes stimulated by electrical pulses was investigated. 45Ca2+ uptake was voltage dependent. Adenosine (1 nM-1 microM) decreased the uptake of 45Ca2+ induced by electrical stimulation (amplitude, 20 V; duration, 400 microseconds; frequency, 10 pulses/s) in a concentration-dependent manner. At a concentration of 1 microM, adenosine almost abolished the 45Ca2+ uptake induced by electrical stimulation (92.9 +/- 5.3% inhibition), but when the calcium uptake was induced by high-K+ (60 mM) medium, the effect of adenosine (1 microM) was smaller (43.8 +/- 5.2% inhibition). The inhibitory effect of 1 microM adenosine on calcium uptake induced by electrical stimulation was antagonized by 1,3-dipropyl-8-p-sulfophenylxanthine (5 microM). The possibility that adenosine interacts with the calcium channels opened by electrical stimulation is discussed.

Adenosine↗
PubMed1991

Solubilized rat brain adenosine receptors have two high-affinity binding sites for 1,3-dipropyl-8-cyclopentylxanthine.

The specific binding of L-N6-[3H]phenylisopropyladenosine (L-[3H]PIA) to solubilized receptors from rat brain membranes was studied. The interaction of these receptors with relatively low concentrations of L-[3H]PIA (0.5-12.0 nM) in the presence of Mg2+ showed the existence of two binding sites for this agonist, with respective dissociation constant (KD) values of 0.24 and 3.56 nM and respective receptor number (Bmax) values of 0.28 +/- 0.03 and 0.66 +/- 0.05 pmol/mg of protein. In the presence of GTP, the binding of L-[3H]PIA also showed two sites with KD values of 24.7 and 811.5 nM and Bmax values of 0.27 +/- 0.09 and 0.93 +/- 0.28 pmol/mg of protein for the first and the second binding site, respectively. Inhibition of specific L-[3H]PIA binding by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (0.1-300 nM) performed with the same preparations revealed two DPCPX binding sites with Ki values of 0.29 and 13.5 nM, respectively. [3H]DPCPX saturation binding experiments also showed two binding sites with respective KD values of 0.81 and 10.7 nM and respective Bmax values of 0.19 +/- 0.02 and 0.74 +/- 0.06 pmol/mg of protein. The results suggest that solubilized membranes from rat brain possess two adenosine receptor subtypes: one of high affinity with characteristics of the A1 subtype and another with lower affinity with characteristics of the A3 subtype of adenosine receptor.

Animals↗
PubMed1991

Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve ending of the rat.

1. The effects of the adenosine analogues, 5'-N-ethyl-carboxamide adenosine (NECA), R-N6-phenylisopropyladenosine (R-PIA), 2-chloroadenosine (CADO), and CGS 21680C on electrically evoked tritium outflow from preparations loaded with [3H]-choline and on evoked endplate potentials (e.p.ps), as well as the ability of the xanthines, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and PD 115,199 to antagonize the effects of the adenosine analogues, were investigated in phrenic nerve-diaphragm preparations. 2. NECA, R-PIA and CADO decreased, in a concentration-dependent manner, the evoked tritium outflow from preparations loaded with [3H]-choline. NECA and R-PIA were about equipotent and more potent than CADO. 3. DPCPX shifted to the right in a near parallel fashion the concentration-response curve for the inhibitory effect of R-PIA on evoked tritium outflow. 4. In the presence of DPCPX, NECA increased, rather than decreased, evoked tritium outflow. PD 115,119 antagonized, in a concentration-dependent manner, this excitatory effect of NECA. 5. CGS 21680C, in low nanomolar concentrations, increased evoked tritium outflow, an effect also antagonized by PD 115,119. 6. CGS 21680C increased, and R-PIA decreased, the amplitude of e.p.ps recorded from preparations paralysed with tubocurarine. Both effects could be observed in the same endplate. 7. It is concluded that both inhibitory (probably A1) and excitatory (probably A2) adenosine receptors coexist at the rat neuromuscular junction, modulating the evoked release of acetylcholine.

Adenosine↗
PubMed1990

2-Chloroadenosine decreases long-term potentiation in the hippocampal CA1 area of the rat.

The effect of the adenosine (ADO) analogue 2-chloroadenosine (CADO) on frequency-induced long-term potentiation (LTP) of the responses evoked by stimulation of the Schaffer fibres and recorded in CA1 area was studied in hippocampal slices of the rat. CADP significantly decreased LTP of the population spikes (PS) (EC50 = 0.28 microM), and LTP of the field excitatory postsynaptic potentials (f.e.p.s.p) (EC50 = 0.33 microM). These effects were reversed by the ADO receptor antagonist 8-phenyltheophylline (8-PT) (2.5 microM). It is concluded that CADO decreases LTP through activation of a xanthine-sensitive ADO receptor.

2-Chloroadenosine↗
PubMed1990

Effect of 5'-(N-ethylcarboxamido)adenosine on adenosine transport in cultured chromaffin cells.

Extracellular adenosine is transported into chromaffin cells by a high-affinity transport system. The action of adenosine receptor ligands was studied in this cellular model. 5'-(N-Ethylcarboxamido)adenosine (NECA), an agonist of A2 receptors, activated adenosine transport. Km values for adenosine were 4.6 +/- 1.0 (n = 5) and 10.2 +/- 3.0 microM (n = 5) for controls and 100 nM NECA, respectively. The Vmax values were 66.7 +/- 23.5 and 170.2 +/- 30 pmol/10(6) cells/min for controls and 100 nM NECA, respectively. The A1 agonist N6-cyclohexyladenosine, the A1 antagonist 8-cyclopentyl-1, 3-dipropylxanthine, and the A1-A2 antagonist 1,3-dipropyl-8-(4-[(2-aminoethyl)amino]-carbonylmethyloxyphenyl)- xanthine did not significantly modify the adenosine transport in this system. Binding studies done with [3H]dipyridamole, a nucleoside transporter ligand, did not show changes in either the number or affinity of transporter sites after NECA treatment. This ligand can enter cells and quantifies the total number of transporters. The binding studies with [3H]-nitrobenzylthioinosine, which quantifies the plasma membrane transporters, showed a Bmax of 19,200 +/- 800 and 23,200 +/- 700 transporters/cell for controls and 100 nM NECA, respectively. No changes in the KD were obtained. The effects of NECA were not mediated through adenylate cyclase activation, because its action was not imitated by forskolin.

Adenosine↗
PubMed1990

Interactions between adenosine and phorbol esters or lithium at the frog neuromuscular junction.

1. Interactions between the effects of adenosine or 2-chloro-adenosine (CADO) and the effects of substances that interfere with the phosphoinositides/protein kinase C transducing system or with the adenylate cyclase transducing system, on endplate potentials (e.p.ps), were investigated. The preparation used was the innervated sartorius muscle of the frog in which twitches had been prevented with high magnesium concentrations. 2. The activator of protein kinase C, 4 beta-phorbol-12,13-diacetate (PDAc), reversibly increased the amplitude and the quantal content of e.p.ps and attenuated the inhibitory effects of adenosine and CADO on e.p.p. amplitude. The affinity of the adenosine receptor antagonist, 8-phenyltheophylline, was not modified by PDAc. 3. The phorbol ester 4 alpha-phorbol-12,13-didecanoate, which does not activate protein kinase C, did not modify either e.p.p amplitude or the inhibitory effect of adenosine on e.p.ps. 4. The inhibitor of protein kinase C, polymyxin B, reversibly decreased the amplitude and the quantal content of e.p.ps, prevented the enhancement caused by PDAc on e.p.p. amplitude, but did not modify the inhibitory effect of adenosine on e.p.ps. H-7, another inhibitor of protein kinases, also decreased e.p.p. amplitude but did not modify the effect of PDAc on the amplitude of e.p.ps. 5. Lithium chloride, which alters phosphoinositide signal transduction by inhibiting the breakdown of inositol phosphates, reversibly increased the amplitude and the quantal content of the e.p.ps. In the presence of adenosine or CADO the effect of lithium on e.p.p. amplitude was markedly attenuated. 6. The activator of adenylate cyclase, forskolin, reversibly increased the amplitude and the quantal content of the e.p.ps. 7. The results suggest that the phosphoinositides/protein kinase C transducing system, but not the adenylate cyclase transducing system, might be involved in the inhibitory effect of adenosine on neuromuscular transmission.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

The inhibitory adenosine receptor at the neuromuscular junction and hippocampus of the rat: antagonism by 1,3,8-substituted xanthines.

1. The ability of 1,3,8-substituted xanthines to antagonize the inhibitory effects of adenosine receptor agonist on the amplitude of nerve-evoked twitches of the rat phrenic-diaphragm and on the amplitude of orthodromically-evoked population spikes, recorded from the CA1 pyramidal cells of rat hippocampal slices, was investigated. 2. 1,3-Dipropyl-8-cyclopenthylxanthine (DPCPX), 1,3-dipropyl-8-(carboxymethyloxyphenyl)xanthine (XCC), 1,3-dipropyl-8-(4-[2-aminoethyl)amino)carbonylmethyloxyphenyl)x ant hine (XAC), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), 8-phenyltheophylline (8-PT), 1,3-diethyl-8-phenylxanthine (DPX) and PD 115,199, in concentrations virtually devoid of effect on neuromuscular transmission, shifted to the right in a near parallel manner the log concentration-response curve for the inhibitory effect of 2-chloroadenosine (CADO) on nerve-evoked twitches of the phrenic-diaphragm. Linear Schild plots with slopes near to unity were obtained for all the xanthines. 3. The order of potency of the xanthines as antagonists of the effect of CADO in the phrenic-diaphragm was DPCPX (Ki = 0.54 nM) greater than XCC (Ki = 10 nM), XAC (Ki = 11 nM), PACPX (Ki = 13 nM) greater than DPX (Ki = 22 nM), 8-PT (Ki = 25 nM) greater than PD 115,199 (Ki = 57 nM). The potency of DPCPX in antagonizing the inhibitory effects of R-N6-phenylisopropyladenosine (R-PIA) and 5'-N-ethylcarboxamide adenosine (NECA) on nerve-evoked twitch response was not statistically different from its potency in antagonizing the inhibitory effect on CADO. 4. In the hippocampal slices, DPCPX, XCC and XAC, used in concentrations virtually devoid of effect on population spike amplitude, shifted to the right in a near parallel manner the log concentrationresponse curve for the inhibitory effect of CADO on the amplitude of the population spikes. The Schild plots were linear with slopes near unity. 5. The potencies of DPCPX (K, = 0.45 nM) and XAC (K, = 11 nM) in antagonizing the inhibitory adenosine receptor at the hippocampus were similar to their potencies for antagonism of the inhibitory adenosine receptor at the phrenic-diaphragm. XCC was only slightly more potent (K, = 5.4 nM) as an antagonist of the adenosine receptor in the hippocampus than in the phrenic-diaphragm. 6. The results suggest that the inhibitory adenosine receptors in the phrenic-diaphragm and in the hippocampus of the rat are similar, and that according to the antagonist potencies, these receptors belong to the A1-adenosine receptor subtype.

Animals↗
PubMed1979

Modification of the cardiotoxic effects of ouabain by acepromazine, tetrodotoxin and magnesium sulphate.

Acepromazine (500 microgram), tetrodotoxin (0.5 microgram) and magnesium sulfate (7.5 mg twice) given intracerebroventricularly increased the doses of ouabain given by continuous intravenous infusion, required to induce arrhythmias and death. Acepromazine (150 microgram kg-1) was also effective when administered intravenously. Acepromazine (1.5 mg kg-1) and tetrodotoxin (4-6 microgram kg-1) given intravenously did not protect against, and even increased, the toxicity of ouabain. Both substances decreased blood pressure and increased heart rate. Tetrodotoxin, but neither acepromazine nor magnesium sulphate given intracerebroventricularly, induced a decrease in the heart rate before ouabain infusion. Acepromazine (500 microgram) and tetrodotoxin (0.5 microgram), but not magnesium sulphate, given intracerebroventricularly, decreased the blood pressure before ouabain infusion. The results are discussed in relation to the effects of those substances and ouabain on the circulation, and to the fact that the cardiac arrhythmias induced by high doses of ouabain and the protection obtained with tetrodotoxin and magnesium sulphate are, at least in part, mediated by the central nervous system.

Acepromazine↗
PubMed1979

Purine effects at the neuromuscular junction and their modification by theophylline, imidazole and verapamil.

Interactions between some substances (theophylline, noradrenaline, imidazole, ouabain and verapamil) and adenosine or adenosine triphosphate (ATP) were examined by recording the twitch tension of partially magnesium blocked phrenic-rat diaphragm preparations stimulated indirectly. Theophylline (an inhibitor of phosphodieterases) prevented and reversed the neuromuscular depression induced either by adenosine or ATP, and these substances antagonized the neuromuscular facilitation caused by imidazole (an activator of phosphodiesterases); noradrenaline and ouabain did not modify and verapamil increased that depression. These results indicate that the putative purine presynaptic receptor is not the ATPase, that it does not appear to operate by implication of cyclic AMP, but that it could mediate a process involved in the reduction of transmitter release by regulating the entry of calcium that follows the depolorization of the motor nerve endings.

Adenosine↗
PubMed1978

Mechanisms of depression of neuromuscular transmission by ATP and adenosine.

1. The effects of ATP in the presence of theophylline and imidazole were investigated on the twitch tension of a partially magnesium blocked rat phrenic nerve-diaphragm preparation. Both theophylline and imidazole facilitate the neuromuscular transmission and prevent the effects of ATP. 2. The effects of adenosine in solutions with low calcium concentrations in the frog-sartorius and in solutions with very low calcium concentrations in the rat-diaphragm were studied on the miniature end-plate potentials. Adenosine caused a similar reduction of the frequency of the miniature end-plate potentials in both low and very low calcium concentrations. 3. The results are discussed in relation to the cyclic AMP and calcium hypothesis.

Action Potentials↗