C. Gros

Bio: C. Gros is an academic researcher from Pasteur Institute. The author has contributed to research in topics: Enkephalinase & Thiorphan. The author has an hindex of 5, co-authored 5 publications receiving 232 citations.

Selective protection of methionine enkephalin released from brain slices by enkephalinase inhibition.

Abstract: Methionine enkephalin release was evoked by depolarization of slices from rat striatum with potassium. In the presence of 0.1 microM thiorphan [(N(R,S)-3-mercapto-2-benzylpropionyl)glycine], a potent inhibitor of enkephalin dipeptidyl carboxypeptidase (enkephalinase), the recovery of the pentapeptide in the incubation medium was increased by about 100 percent. A similar effect was observed with the dipeptide phenylalanylalanine, a selective although less potent enkephalinase inhibitor. Inhibition of other known enkephalin-hydrolyzing enzymes--aminopeptidase by 0.1 mM puromycin or angiotensin-converting enzyme by 1 microM captopril--did not significantly enhance the recovery of released methionine enkephalin. These data indicate that enkephalinase is critically involved in the inactivation of the endogenous opioid peptide released from striatal neurons.

Inhibition de la libération évoquée de (Met2)enképhaline de coupes de globus pallidus en présence de thiorphan et de bestatine

Abstract: La (Met 5 ) enkephaline liberee a partir de coupes de globus pallidus de rat par le potassium est hydrolysee a 85% avant d'atteindre le milieu d'incubation. L'addition de thiorphar et de bestatine, deux inhibiteurs de peptidases, previent totalement cette degradation mais s'accompagne d'une diminution significative de liberation. La liberation etant retablie en presence d'un antagoniste des opioides, la naloxone en concentration moderee, l'existence d'un mecanisme d'auto-inhibition de la liberation d'enkephaline est proposee

Ontogenesis of enkephalinergic systems in rat brain

Abstract: Summary Post-natal changes in the levels of the two enkephalins in opiate receptors and in enkephalin-degrading peptidases were evaluated in cortex and striatum In both regions Met- and Leu-ENK levels increased in parallel, adult levels (4-fold neonatal ones) being reached by 3 weeks Striatal ENK dipeptidyl carboxypeptidase increased 3-fold between 0–20 days, then decreased by 40% to reach adult activity The development of angiotensin-converting enzyme was distinct, confirming that different enzymes are involved

The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice

Abstract: There is both theoretical and therapeutic interest in establishing whether the signals conveyed by the enkephalins are turned off under the action of a specific peptidase which might, in this case, represent a target for a new class of psychoactive agents. Enkephalinase, a dipeptidyl carboxypeptidase cleaving the Gly3-Phe4 bond of enkephalins and distinct fropm angiotensin coverting enzyme (ACE), might be selectively involved in enkephalinergic transmission. It is a membrane-bound enzyme whose localization in the vicinity of opiate receptors in the central nervous system is suggested by parallel regional and subcellular distributions as well as by the effects of lesions. Such a role is further supported by the ontogenetic development of enkephalinase, its substrate specificity accounting for the increased biological activity of several enkephalin analogues and its adaptive increase following chronic treatment with morphine. To investigate the functional role of this enzyme further, we have designed a potent and specific enkephalinase inhibitor. We report here that this compound, thiorphan [(DL-3-mercapto-2-benzylpropanoyl)-glycine; patent no. 8008601] protects the enkephalins from the action of enkephalinase in vitro in nanomolar concentration and in vivo after either intracerebroventricular or systemic administration. In addition, thiorphan itself displays antinociceptive activity which is blocked by naloxone, an antagonist of opiate receptors.

Differential ontogeny of multiple opioid receptors (mu, delta, and kappa)

Abstract: We investigated the postnatal ontogeny of opioid receptors in rat brain under assay conditions which, when combined with computerized analysis, effectively reflect the developmental profile of high affinity binding to mu, delta, and kappa subpopulations. Concentrations of mu sites were assessed with the selective ligand 3H-[D-ala2,mePhe4,gly-ol5]enkephalin (DAGO). The other two sites were analyzed in binding assays with less selective radioligands but in the presence of specific unlabeled ligands which suppress cross-reactivity. We utilized 3H-[D-ala2,D- leu5]enkephalin (DADL) in the presence of 10 nM DAGO to label delta sites and 3H-ethylketocyclazocine (EKC) in the presence of 100 nM DADL + 100 nM [D-ala2,mePhe4,Met(0)ol5]enkephalin to detect kappa receptors. After birth, the density (femtomoles per milligram of wet weight) of mu sites declined for several days and then rose sharply over the next 2 weeks, increasing 2-fold by adulthood. Delta (delta) sites appeared in the second week postnatal and increased more than 8-fold in the next 2 weeks. Levels of kappa receptors were relatively low at birth and increased slowly (2-fold, overall). Computerized analyses of binding data revealed that DAGO and DADL were binding to single populations of sites throughout the postnatal period. DAGO and EKC affinities did not fluctuate in this period, whereas DADL affinities were low for the first week and then rose to adult levels. In summary, mu, kappa, and delta receptors exhibit differential postnatal developmental profiles. The former two are present at birth, whereas the latter appears in the second week. The postnatal increase for all three sites appear to be preceded by the previously demonstrated emergence of opioid peptides.