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Biomedical subjects

R M Gaion

Publications and source records attributed to R M Gaion.

At least 37 records · Page 2Linked to original sources
PubMed1988

A reexamination of the effects induced by adenosine and its degradation products on rat fat cell lipolysis.

The effects of adenosine and of some products of its metabolic degradation on lipolysis were studied in rat fat cells isolated from epididymal adipose tissue. Basal glycerol release was not affected by adenosine and by uric acid, but it was significantly increased by inosine (1-100 microM) and by hypoxanthine (10-100 microM). Adenosine was more effective than inosine in antagonizing the lipolytic response of fat cells to theophylline. Also hypoxanthine and uric acid exerted a very potent, noncompetitive antagonism towards theophylline. Norepinephrine-induced lipolysis was inhibited by adenosine, hypoxanthine and uric acid approximately to the same extent, while inosine was ineffective at this level. Adenosine deaminase (0.5 U/ml) increased basal as well as theophylline- and norepinephrine-induced lipolysis. Moreover, adenosine deaminase enhanced the lipolytic rate in cells incubated with low (0.1, 1 microM) and, to a lesser extent, with high (10, 100 microM) inosine concentrations. These results suggest that inosine is the adenosine metabolite that may accumulate in the incubation medium following fat cell treatment with adenosine deaminase, thus contributing to the stimulatory effects of this enzyme on lipolysis.

Adenosine↗
PubMed1988

Low- and medium-dose diltiazem in chronic atrial fibrillation: comparison with digoxin and correlation with drug plasma levels.

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 +/- 0.43 vs 1.05 +/- 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 +/- 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (-17.2% and -14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 +/- 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The response of isolated guinea-pig aorta to amrinone.

1. In helically cut strips of aorta from reserpine-treated guinea-pigs, cumulative concentrations (30 microM, 0.3 mM and 3 mM) of amrinone progressively reduced the basal tone of the preparations and relaxed the smooth muscle contracted by 1 microM noradrenaline or by 20 mM K+. 2. The relaxing effect was completely suppressed by tissue pretreatment with adenosine deaminase (1 U ml-1). 3. Relaxation induced by amrinone was not affected by 50 microM indomethacin or by 0.1 mM 8-phenyltheophylline and was potentiated by 5 microM quinidine. 4. Like amrinone, exogenous adenosine reduced the basal tone of the guinea-pig aorta strips and relaxed the preparations contracted by 1 microM noradrenaline or by 20 mM k+ in a concentration-dependent manner. 5. The relaxing activity of exogenous adenosine was not affected by 50 microM indomethacin, was potentiated by 5 microM quinidine and was partially antagonized by 0.1 mM 8-phenyltheophylline. 6. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone on guinea-pig aorta strips, but the specific mechanism of amrinone-adenosine interaction remains to be elucidated.

Adenosine↗
PubMed1988

Involvement of P1-purinoreceptors in the relaxing effect of adenosine in rat duodenum.

1. In isolated segments of rat duodenum, adenosine (50 microM-2 mM) caused a very rapid and short-lasting relaxation that was associated with a marked decrease in the amplitude of spontaneous contractions. 2. Theophylline (0.1-0.8 mM) and 8-phenyltheophylline (1-10 microM) antagonized, in a concentration-dependent manner, the effects of 0.3 mM adenosine on smooth muscle tension and spontaneous activity. 3. The concentration-response curves for adenosine (50 microM-2 mM) were progressively shifted to the right by increasing concentrations of theophylline and of 8-phenyltheophylline, with no change in the maximum effect. 4. 8-Phenyltheophylline (5 microM) did not affect relaxations induced by noradrenaline (0.5 microM) and by isoprenaline (5 nM). 5. These results indicate that the effects exerted by adenosine on rat duodenum are mediated by P1-purinoreceptors.

Adenosine↗
PubMed1988

Negative and positive influences exerted by purine compounds on isolated guinea-pig atria.

1. In spontaneously beating atria isolated from reserpine-treated guinea-pig adenosine, AMP, ADP, ATP (2 microM) and alpha, beta-methylene ATP (0.4 microM) induced a dual effect: a short lasting negative response, characterized by a reduction in contractile force and in frequency rate, followed by a positive phase of increased inotropism and chronotropism. N6-phenylisopropyladenosine (5 nM) induced only the depressant effects whereas inosine (2 microM) was completely inactive. 2. The early, negative influences were antagonized by 8-phenyltheophylline (0.5-10 microM), an alkylxanthine that competes with purines for P1 receptors. 3. The late, positive response was potentiated by 8-phenyltheophylline (0.5-10 microM) and suppressed by quinidine (5 microM), that blocks the effects of adenine compounds mediated by P2 receptors. 4. In spontaneously beating as well as in electrically driven atria, desensitization of P2 purinoceptors by long lasting exposure to alpha, beta-methylene ATP (8 microM) abolished the late positive response to ATP. In preparations treated with both alpha, beta-methylene ATP and 8-phenyltheophylline, ATP was ineffective. 5. These results suggest that, besides P1 receptors, P2 receptors are also present in guinea-pig atria, mediating stimulatory effects of adenine compounds.

Adenine Nucleotides↗
PubMed1987

Target sites for the inhibition of prostacyclin effect in guinea-pig ileum.

In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI2) (1 mumol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 mumol/l, to low temperature (20 degrees C) and to atropine (30 nmol/l). Half maximum contractions evoked by PGI2 (20 nmol/l) were abolished by TTX and by low temperature, which did not modify the response to exogenous acetylcholine (ACh), as well as by atropine. Procaine (5-500 mumol/l) caused a concentration-dependent inhibition of contractions induced by PGI2 (20 nmol/l and 1 mumol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 mumol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI2 20 nmol/l greater than PGI2(1) mumol/l greater than ACh 0.4 mumol/l. In preparations exposed to TTX or to low temperature procaine (50 mumol/l) did not affect the residual response to PGI2 (1 mumol/l). Quercetin (1 and 5 mumol/l) inhibited the effect of PGI2 and, at higher concentrations, it also caused partial depression of the responses to ACh. Quercetin did not alter TTX-resistant and low temperature-resistant contractions induced by PGI2 1 mumol/l. Carbonyl cyanide-trifluoro-methoxyphenyl hydrazone (FCCP) (0.1-1 mumol/l) reduced the effect of PGI2 and of ACh to approximately the same extent and inhibited the residual response to PGI2 1 mumol/l in preparations treated with TTX or expressed to low temperature. The present results show that PGI2, besides acting on cholinergic neurons, also exerts a direct effect on smooth muscle cells and FCCP can be used to block this effect. In contrast procaine and quercetin selectively inhibit the ACh-mediated component of PGI2 action.

Acetylcholine↗
PubMed1987

Verapamil-induced changes in digoxin kinetics in cirrhosis.

The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.

Adult↗
PubMed1987

The role of calcium in amrinone action on intestinal smooth muscle.

In the guinea-pig isolated ileum amrinone (3 microM to 0.3 M) induced transient, dose-dependent contractions which were followed by pronounced relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). The contractile effect was potentiated by eserine and abolished by scopolamine. Verapamil, at concentrations (0.1-1 microM) that did not affect basal tension of the preparations or the contractile response to exogenous acetylcholine, selectively reduced amrinone-evoked contraction, while the relaxing component was abolished by verapamil concentrations (5-10 microM) that per se reduced muscle tension as well as acetylcholine-induced contraction. Similarly, when external Ca2+ concentration was reduced from 2.5 to 1.25 and 0.5 mM, the contractile component of amrinone effect was markedly reduced, while relaxation was not significantly altered. Any further decrease of Ca2+ content in the superfusion medium (0.25 to 0 mM) also reduced the relaxing effect of amrinone and the response of the ileum to exogenous acetylcholine. The present results indicate that in guinea-pig ileum amrinone-induced contractions are sustained by acetylcholine release as well as by Ca2+ entry into smooth muscle cells through verapamil-sensitive channels, while other Ca2+ pools may play a role in the relaxing effect of the drug.

Acetylcholine↗
PubMed1987

Influence of prostacyclin on the antilipolytic effect of nicotinic acid in rat fat cells: a comparison with adenosine deaminase and theophylline.

Isolated rat fat cells were incubated at pH 8.5 in order to delay PGI2 inactivation. Nicotinic acid, at concentrations lower than 2 mM was ineffective in antagonizing the stimulation of lipolysis induced by norepinephrine (2 microM). The potentiation of norepinephrine effect due to PGI2 (0.1 microM) was abolished by 0.1 mM nicotinic acid and, at higher concentrations of the drug, the rate of the process fell below the one measured in the absence of PGI2, with a resulting decrease of the response to norepinephrine. Nicotinic acid (0.04-0.4 mM) antagonized the stimulation of lipolysis caused by adenosine deaminase (0.5 U/ml) or by theophylline (0.5 mM) and the potentiation of norepinephrine effect due to adenosine deaminase. In cells treated with adenosine deaminase (0.5 U/ml) or with theophylline (0.5 mM), PGI2 (40 nM) inhibited the lipolytic effect of norepinephrine (5 microM) and nicotinic acid acted synergistically with PGI2 at this level. These results indicate that the antilipolytic action of nicotinic acid is influenced by endogenous adenosine and is increased by PGI2.

Adenosine Deaminase↗
PubMed1987

Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects.

The effect of amiodarone on oral and intravenous pharmacokinetics of digoxin was studied in healthy volunteers. A single 0.5-mg dose of digoxin was administered orally to three subjects both before and after 2 weeks of oral amiodarone (200 mg daily), while three subjects received a 0.5-mg intravenous dose of the glycoside under the same experimental conditions. Two other subjects were given both oral and intravenous doses of digoxin at different times, in the absence and in the presence of amiodarone. After oral digoxin treatment, amiodarone increased peak serum concentration, total area under the serum concentration-time curve (AUC), and 5-day urinary recovery of the glycoside, without changes in peak time and absorption rate constant. During the intravenous study, no significant change occurred in AUC and urinary recovery after amiodarone administration. Absolute bioavailability, for the two subjects who received both oral and intravenous digoxin, increased by 36 and 43%, respectively, after amiodarone treatment. Bioavailability derived from the mean values of oral and intravenous AUCs was 33% greater with amiodarone treatment. Apparent volume of distribution and systemic, extrarenal, and renal clearances of oral digoxin were not modified by amiodarone, when corrected for the bioavailability factor. Amiodarone had no effect on these pharmacokinetic parameters during the intravenous study with the glycoside. Our data indicate that increased oral bioavailability is the most relevant change in digoxin pharmacokinetics during the interaction with amiodarone and this can account for the increase in the glycoside concentrations.

Administration, Oral↗
PubMed1987

Possible role of adenosine in the relaxant effect of amrinone on guinea-pig ileum.

In isolated segments of guinea-pig ileum, amrinone (0.3 mM-0.3 M) caused a transient contraction followed by a concentration-dependent relaxation. Theophylline (0.1-0.5 mM) mimicked the effects of amrinone but apparently inhibited relaxation induced by the latter. However the total decrease of muscle tension measured in preparations exposed to amrinone before and after theophylline treatment was quantitatively comparable. Dipyridamole (0.1 microM) potentiated the relaxing effect of amrinone. The stimulatory response of the ileum to high concentrations of adenosine (10-50 mM) was abolished by amrinone. In preparations treated with adenosine deaminase (10 U/ml) the basal tone was decreased and both amrinone and theophylline were ineffective. In rat ileum, amrinone exerted a marked relaxing effect that was abolished by adenosine deaminase. Thus amrinone appears to cause relaxation of intestinal smooth muscle from different species by hindering the stimulatory effect of endogenous adenosine. The possible intracellular localization of the amrinone-adenosine interaction site is discussed.

Acetylcholine↗
PubMed1987

Amrinone action on guinea-pig isolated stomach fundus.

In the guinea-pig stomach fundus strips, set in cascade, amrinone (3 microM to 0.3 mM) induced contractions which were followed by relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). Contractions were transient and scarcely related to the drug concentration used, whereas relaxation was the most pronounced and concentration-dependent effect. The transient contraction elicited by amrinone was abolished by scopolamine, indicating activation of cholinergic receptors, but it was unaffected by low temperature or hemicholinium-3. The relaxing effect induced by amrinone was unaffected by low temperature, by the receptor inhibitors used (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine) and by indomethacin. It was potentiated by dipyridamole (0.1 microM) and completely suppressed by tissue pretreatment with adenosine deaminase (10 U/ml). Inhibition of this effect was also obtained by reducing Ca2+ concentration in the perfusion fluid or by pretreating the preparations with verapamil. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone and the requirement of Ca2+ influx through plasma membrane for this effect.

Adenosine↗