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Biomedical subjects

H Laborit

Publications and source records attributed to H Laborit.

At least 19 recordsLinked to original sources
PubMed1992

Variations of lipid profile in animals caused by adenosine analogs: N6 (amido-3-propyl) adenosine hydrochloride and (carboxamido-3-propylamino)-6-(triproprionyl) 2',3',5'beta (D-ribosyl)-9-purine.

N6-substituted adenosine analogues are powerful inhibitors of lipolysis in the adipose tissues of animals and humans, because of their agonist effect on A1 purine receptors. Using a model of hypertriglyceridemia provoked by intravenous injection of Triton WR 1339, we observed that Agr 529 [N6(amido-3-propyl)adenosine hydrochloride] at 2 mg.kg-1 intravenous in rabbits, and intraperitoneally and orally in rats led to a return of the levels of circulating triglycerides to normal values. In addition, Agr 529 and its prodrug, Agr 540 [(carboxamido-3-propylamino)-6-(triproprionyl)2', 3',5'beta(D-ribosyl)-9-purine] administered to rats at 3 and 30 mg.kg-1, respectively, returned plasma triglyceride concentrations to normal levels. Intravenous administration of Agr 529 to normal rats led to decreased concentrations of plasma fatty acids, phospholipids, triglycerides and total cholesterol as a function of dose. The decrease began at 0.1 mg.kg-1 and was highly significant at 3 mg.kg-1. In the same conditions, the intraperitoneal administration of Agr 529 caused a dose-dependent hypolipemia. There was no apparent effect on cholesterol and on the triglycerides of high density lipoproteins. A kinetic study showed that the antilipemic effect of Agr 529 intravenously injected at 3 mg.kg-1 began 30 minutes after the injection with a maximum effect at 2 hours. The effect persisted up to 8 hours after injection. The present results show that the administration of Agr 529 and Agr 540 to normal animals causes hypolipemia (decrease in fatty acids, phospholipids, triglycerides and cholesterol) and restores induced hypertriglyceridemia. These effects may be attributed to an interaction of the molecules with A1 purinergic receptors of adipose tissue.

Adenosine↗
PubMed1991

Protective effects of gamma-hydroxybutyrate on alloxan induced diabetes in mice.

Gamma-hydroxybutyrate (GHB) administered to mice prior to alloxan antagonizes its diabetogenic action in a dose dependent fashion and up to 96 hours after injection. Results are discussed on the basis of free radical formation by alloxan and of the metabolic property of GHB which is known to increase the rate of operation of the pentose phosphate pathway.

Alloxan↗
PubMed1990

Chronic stress and memory: implication of the central cholinergic system.

Restraint stress for ten days (two times two hours daily) induces a hypersensitivity of the central cholinergic system, reflected by antagonism to amnesia induced by scopolamine at 0.1 mg/kg in a passive avoidance test and by hypersensitivity to the hypothermic effect of oxotremorine at 1 mg/kg. A restraint stress for 30 days, on the other hand, diminishes animal retention in the passive avoidance test and causes a hyposensitivity to oxotremorine-induced hypothermia, reflecting a hypoactivity of the central cholinergic system. An acute 24-hour stress causes no change. The relationship between chronic stress and associated memory deficits is discussed.

Animals↗
PubMed1990

Action of N6(amido-3-propyl) adenosine hydrochloride (Agr 529) on plasma corticosterone levels in rats.

N6(amido-3-propyl) adenosine (Agr 529) has central properties analogous to those of adenosine. It increases plasma corticosterone levels in rats as a function of dose and of time. A plateau is reached at the dose of 10 mg.kg-1 one hour after intraperitoneal injection. Treatment with a blocker of adenosine receptors, 8-(p-sulfophenyl)-theophylline, which does not cross the blood-brain barrier, inhibits the increase of plasma corticosterone induced by Agr 529. This increase is also absent in hypophysectomized rats and in rats receiving Agr 529 intracerebroventricularly. Thus it is consistent to believe that Agr 529 increases plasma corticosterone in normal rats by acting on adenosine A2 receptors in the pituitary.

Adenosine↗
PubMed1990

Changes in plasma catecholamine levels after the intraperitoneal and intracerebroventricular administration of adenosine analogues and of clonidine in conscious rats.

When an adenosine analogue, N6-(amido-3-propyl) adenosine hydrochloride (Agr 529) is administered systemically, it causes a substantial release of epinephrine (E) by the adrenal medulla with no change in plasma norepinephrine (NE) levels. Low doses of N6-R-phenylisopropyl adenosine (L-PIA), an agonist of adenosine A1 receptors, has no significant effect on plasma epinephrine levels, which are increased by high doses of the analogue. Low doses of 5'-N-ethylcarboxamido-adenosine (NECA), an agonist of adenosine A2 receptors, however, lead to increases. The intracerebroventricular (icv) administration of Agr 529 leads to a significant decrease in plasma NE without affecting E levels. This action is synergistic with that of clonidine icv. The mechanism of central action of this effect is discussed. It can be admitted that the inhibitory effect of adenosine analogues icv occurs via an inhibition of the posterolateral hypothalamus and the locus coeruleus, although we cannot rule out an action on more rostral-situated brain regions. The authors suggest that the central effect of Agr 529 results primarily from the inhibition of central acetylcholine release caused by adenosine analogues and review experimental arguments enabling this hypothesis to be supported. On the other hand, the considerable release of plasma epinephrine seen when adenosine analogues are administered systemically can be attributed to their stimulation of ACTH secretion by the pituitary and the increase in glucocorticoids in the adrenal medulla, as a result of the existence of the cortico-medullary portal system. These glucocorticoids stimulate phenylethanolamine-N-methyltransferase, which transforms norepinephrine to epinephrine.

Adenosine↗
PubMed1989

Brain tyrosine increases after treating with prodrugs: comparison with tyrosine.

After mice had been treated with L-tyrosine, O-phospho-L-tyrosine, L-tyrosine methyl ester or N-acetyl-L-tyrosine, tyrosine was assayed by HPLC coupled with fluorometric detection. O-Phospho-L-tyrosine behaved as a tyrosine prodrug after its hydrolysis by acid and alkaline phosphatases. After the intraperitoneal administration of O-phospho-L-tyrosine or the methyl ester, there was a substantial increase in bioavailability in terms of the effect of tyrosine. The two prodrugs were as powerful as tyrosine following oral administration. N-Acetyl-L-tyrosine was the least effective prodrug tested. The stability, solubility and bioavailability of O-phospho-L-tyrosine are consistent with proposing it for use as a tyrosine prodrug. In addition, it can be used parenterally. The use of a tyrosine aminotransferase inhibitor is necessary for limiting the hepatic breakdown of tyrosine and for increasing its bioavailability.

Animals↗
PubMed1988

[The inhibition of action. Interdisciplinary approach of its mechanisms and physiopathology].

The author recalls his group's work during the three past decades and how, starting from the study of traumatic states, he established the distinction between shock and stress, physiologically and biologically speaking. According to him, stress supposes a memory process, i.e. the learning of the inefficiency of action in controlling the environmental characteristics. This learning involves cerebral areas and nerve tracks which, as behavioural consequences produce action inhibition. In the neurophysiological field, he underlines the importance, for these mechanisms, of the cortex, dorsal Ammon's horn, lateral tonsil and subthalamic nucleus. He shows why it seems obvious that the mediators of the action inhibiting system are acetylcholine and serotonin. He also recalls the many experimental facts which allow to say that the action inhibiting system is responsible for the release of the hypothalamic-hypophyseal-adrenocortical reaction and of the peripheric sympathetic adrenergic reaction to aggression. He finally shows the function of these two systems where the main pathological accidents originate. He also stresses the discovery and the introduction in the therapeutical paraphernalia of a new molecule minaprine, which he considers as inhibiting action inhibition, and as such, as an indirect anti-depressive drug. The pathology, which is said psychosomatic, thus becomes a pathology of action inhibition, where unconscious memory of past interdictions and failures, relates the subject and his present reaction to environment, to his whole psycho-social past.

Acetylcholine↗