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J Marchand

Publications and source records attributed to J Marchand.

At least 55 records · Page 3Linked to original sources
PubMed1982

Studies of covalent adducts of NAD(P) and enolizable ketones as specific glutamate dehydrogenase inhibitors.

Structural analogues of the reduced coenzymes, NADH or NADPH, of dehydrogenases are prepared by addition of carbonyl compounds including: pyruvate, alpha ketoglutarate, oxaloacetate, butyraldehyde, acetaldehyde and acetone, to the oxidized coenzymes NAD(P). Some of the adducts obtained are specific inhibitors of the glutamate dehydrogenase. The specificity is related to the carbonyl compound used. The high selectivity of the dehydrogenases for adducts is evidenced by inhibition studies of NAD(P)-pyruvate and NAD(P)-alpha ketoglutarate adducts on both activities of glutamate dehydrogenase. The inhibitions are competitive with the reduced coenzymes and the oxidized substrates: adducts could be considered as structures closely related to the ternary complexes of the dehydrogenase.

Animals↗
PubMed1982

NAD(P) adducts as protective agents against glutamate dehydrogenase inactivation by pyridoxal 5'-phosphate: a tool for the study of oxidized coenzyme activated state in enzymatic evolutive and abortive complexes.

Glutamate dehydrogenase is reversibly inhibited by the reaction of 1 mole of pyridoxal 5'-phosphate per mole of subunit of the enzyme polypeptide chain. We have shown that NAD(P) adducts as well as NMNH protect the glutamate dehydrogense against this reversible inactivation in the same way as reduced coenzymes. These data lead to the conclusion that it is the 1,4-dihydronicotinamide structure that is responsible for protecting the enzyme. NAD+ and NMN+ do not protect the enzyme, but in the presence of the oxidized substrate NAD+ became a good protecting agent whereas NMN+ remained ineffective. To explain the protection exerted by NAD+ in the presence of oxidized substrate, a transient activated form of the oxidized coenzyme with a 1,4-dihydronicotinamide structure and a positive charge on the C-4 atom is postulated.

Animals↗
PubMed1981

Calcium deprivation enhances glucagon release in the presence of 2-ketoisocaproate.

The effect of calcium deprivation upon glucagon and insulin release was studied in the rat pancreas perfused in the presence of 2-ketoisocaproate (10 mM). Control perfusions were conducted in the presence of glucose (11.1 mM). In the presence of 2-ketoisocaproate, the decrease in the extracellular concentration of calcium provoked a dramatic, but reversible, enhancement of glucagon release. Such a secretory response was similar in pattern to that seen upon calcium omission in the presence of glucose. Bio-Gel P-30 chromatographic studies showed that only true glucagon (mol wt, 3500) was liberated in the pancreatic effluent during the period of calcium deprivation. On the other hand, the secretion of insulin induced by 2-ketoisocaproate was, like that elicited by glucose, markedly inhibited upon the decrease in extracellular calcium concentration (80% and 65% inhibition, respectively). The results are interpreted in support of the hypothesis that calcium may play an inhibitory role in the control of glucagon release. It is suggested that such a role is somehow linked to the metabolism of exogenous nutrients in the A2 cells.

Animals↗
PubMed1980

Effects of morphine on sensory-evoked responses recorded from central gray, reticular formation, thalamus, hypothalamus, limbic system, basal ganglia, dorsal raphe, locus ceruleus, and pineal body.

Field potential recordings of acoustic and photic-evoked responses were obtained from 15 brain sites of freely behaving unanesthetized rats previously implanted stereotaxically with permanent electrodes. Several dosages of morphine (1, 5, 10, 30, and 50 mg/kg) were examined. The activities recorded from all the structures in this study, except the cochlear nucleus (CoN), were affected by morphine. Different sensitivities to morphine threshold were observed between structures, and several structures exhibited dose-related patterns (ventromedial hypothalamus (VMH), caudate nuucleus (CN), central gray (CG), hippocampus (Hipp), and lateral septum (Spt)). Several brain sites, after the initial dose of morphine, did not recruit more responses to subsequent doses of the drug, ie, exhibited all-or-none responses (pineal body (PB), medial thalamus (MTh), anterior hypothalamus (AH), mesencephalic reticular formation (MRF), and the dorsal raphe (DR)). In some structures, morphine induced increases in the response amplitudes, while in other sites decreases in response amplitudes were elicited. Biphasic responses, ie, increases in response amplitude after low doses of the drug and decreases in response amplitude after higher dosages, were also observed (VMH, CN, DR, CG, and MRF). The acoustic-evoked responses were affected by morphine more than the photic responses. The present observations indicated that 1) morphine exerts effects in many parts of the central nervous system (CNS); 2) some structures are more sensitive to morphine than others; 3) only a few structures exhibit dose-related patterns and, thus, may represent sites of direct morphine action; 4) some structures exhibit all-or-none responses; and 5) morphine depressed activity in some structures and increased activity in others, ie, morphine elicited different effects in different structures.

Acoustic Stimulation↗
PubMed1980

Inhibition of cyclic nucleotide accumulation following hippocampal tetanic potentiation: effects of diazepam.

Biochemical studies on the hippocampus of acutely prepared rabbits revealed more than twofold increases in cyclic GMP levels following tetanic potentiation of the pathway from the medial septal region to CA1 pyramidal cells. Diazepam, administered intravenously, prevented the elevation in cyclic GMP levels in this region and also attenuated the post-tetanic potentiation seen following the presentation of trains at frequencies within theta rhythm. The results imply a modulatory role for cyclic nucleotides in the enhancement of pyramidal cell excitability and suggest that the biochemical mechanism for the psychoactive benzodiazepines may well include the suppression of cyclic GMP levels.

Animals↗
PubMed1980

Mode of action of clonidine upon islet function: dissociated effects upon the time course and magnitude of insulin release.

Clonidine (0.08 to 80.0 ng/ml) caused a dose-related inhibition of glucose-stimulated insulin release, but failed to affect glucose oxidation, glucose-stimulated 45Ca net uptake, and adenylate cyclase activity in isolated rat islets. Phentolamine antagonized the effect of clonidine upon insulin release. Despite profound inhibition of insulin secretion, the drug failed to affect the time course for the changes evoked by glucose in either 45Ca fractional outflow rate from perfused islets or insulin release from the isolated perfused pancreas. The latter changes were multiphasic, revealing an initial secretory peak, a period of low secretory activity, and a second secretory elevation before establishing a period characterized by a steadily and slowly increasing insulin output. In the clonidine-treated islets, the secretory rate was not significantly different from the basal value during the period after the initial secretory response. Thus, despite continuous stimulation with glucose, insulin release appears as a discontinuous phenomenon, even when little insulin is secreted during the initial phase of stimulation.

Adenylyl Cyclases↗
PubMed1979

The effect of muscimol on hippocampal pyramidal cells.

The effects of muscimol on rabbit hippocampal pyramidal cell firing were studied and compared after iontophoretic, topical, and intravenous administration of the drug. All modes of application resulted in a bicuculline-sensitive, strychnine-insensitive, depression of the monosynaptically activated population spike evoked by micro-stimulation of the contralateral hippocampal field. These findings indicate that systemically administered muscimol selectively activates hippocampal GABA receptors suggesting that this compound may be useful for studying limbic system physiology.

Action Potentials↗
PubMed1979

Interactions of alpha-ketoisocaproate, glucose and arginine in the secretion of glucagon and insulin from the perfused rat pancreas.

The effects of alpha-ketoisocaproate (KIC, 10 mmol/l) on glucagon and insulin release were studied in the in vitro perfused rat pancreas. The experiments were performed at low glucose concentration (3.3 mmol/l) in the absence or presence of arginine (10 mmol/l). In all the experiments KIC induced a marked and not rapidly reversible inhibition of glucagon release. This inhibition was more pronounced in the absence (76 percent) than presence of arginine (61 percent). These inhibitory patterns closely duplicated those which were seen in parallel experiments which included a rise in the concentration of glucose (from 3.3 to 11.1 mmol/l). KIC was also a potent stimulator of insulin release. The results are compatible with the view that the intracellular metabolism of KIC and glucose plays an essential role in the regulation of glucagon release by exogenous substrates.

Animals↗
PubMed1979

Calcium dependency of glucagon release: its modulation by nutritional factors.

The calcium dependency of glucagon release by the perfused rat pancreas was investigated in the presence of different nutrients: glucose, arginine, and a mixture of "fumarate + glutamate + pyruvate" (FGP, 5 mM of each salt). At a 3.3 mM glucose concentration, FGP-induced glucagon release was inhibited by the removal of calcium or addition of verapamil. At a higher glucose concentration (16.6 mM), the glucagonotropic action of FGP was again inhibited by verapamil, but the removal of extracellular calcium enhanced transiently glucagon release. Comparable results were obtained when arginine (10 mM) instead of FGP was used to stimulate the alpha cell. These findings suggest that the glucagonotropic effect of FGP or arginine depends on the availability and inward transport of calcium, whereas extracellular calcium per se may be required for glucose to be sensed by the alpha cell as an inhibitor of glucagon secretion. Thus, the nutritional environment offered to the alpha cell may condition the expression of the different mechanisms involved in the control of glucagon release by calcium.

Animals↗
PubMed1978

The role of calcium in glucagon release. Studies with verapamil.

The role of calcium transport into the pancreatic A2-cell in release of glucagon was studied in the perfused in vitro rat pancreas exposed to the organic calcium-antagonist verapamil (10 and 20 microns). As judged by the inhibitory effect of verapamil, a sufficient influx of calcium was required for glucagon release to be stimulated by either arginine (10 mM) or a lowering of the glucose concentration from 16.6 to 3.3 mM. However, such was not the case for glucose to inhibit the release of glucagon or when the A-2-cell was established in a stimulated state during prolonged exposure to a low, 3.3 mM, glucose concentration. These findings suggest that the role of inwardly directed transport of calcium in the secretory process of the A2-cell is of a complex nature, being dependent on the type of stimulus employed (arginine or glucose) and, in the case of glucose, on the static or dynamic state of the cell. The intimate mechanisms by which calcium exerts such complex effects on the secretory process in the A2-cell remain to be elucidated.

Animals↗
PubMed1977

[Otitic tetanus].

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Facial Muscles↗