María Dolores Mayas-Torres⁽¹⁾, José Manuel Martínez-Martos⁽²⁾, María Jesús Ramírez-Expósito⁽³⁾, María Jesús García-López⁽⁴⁾, Isabel Prieto-Gómez⁽⁵⁾, Garbiñe Arechaga-Maza⁽⁶⁾, Manuel Ramírez-Sánchez^{(7)
(1)(2)(4)(5)(6)(7)}Unit of Physiology. University of Jaén - Jaén. Spain
⁽³⁾Unit of Physiology. University of Jaen - Jaén. Spain

	[Endocrinology]	[Neuroscience]	[Pharmacology]	[Physiology]	[Toxicology]

DISCUSSION AND CONCLUSIONS

In this work, we show the ability of ethanol to modify pGluAP activity. Ethanol induces an inhibition of this activity. This inhibition is independent of the presence of calcium in the artificial CSF on basal conditions. In depolarized conditions, pGluAP activity is not affect when calcium is included in the artificial CSF. On the other hand, pGluAP activity is lower when the stimulation with K+ 25 mM occurrs in a calcium-free artificial CSF. Therefore, depolarization induces a calcium-dependent behaviour in pGluAP activity. This differences occurs also when ethanol is administrated at different doses. So in presence of calcium presence in the artificial CSF, ethanol induces an inhibition inversely proportional to the concentration of ethanol used. In a calcium-free artificial CSF, the inhibition induced by ethanol is proportional to the ethanol concentration used.

The pGluAP enzyme is a peptidase widely distributed in fluids and tissues. To date, three distinct forms of pGluAP have been observed. The first, pGluAP type I is localized to the cytosolic compartment ^(6,7,8), and has a broad pyroglutamyl-substrate specificity, including TRH, GnRH, neurotensin, bombesin ⁽⁷⁾. The pGluAP type II has been shown to be a membrane-bound enzyme with a high specificity to the TRH neurohormone TRH ^(9,10). A third pGluAP, called thyroliberinase, has also been observed in the serum, and its biochemical characteristics are very similar to those of pGluAP type II ^{(11,12,13,14)}.

Although the hydrolytic action on peptide or artificial substrates of these different types of pGluAP has been extensively studied, their actual physiological role is not well defined. In this work is shown that the administration in vitro of ethanol modifies this enzymatic activity (it is inhibited), and that modification is depending on the calcium levels on the artificial CSF. It has been described the intracerebroventricular administration of peptides related to the pGluAP (neurotensin and bombesin) to mice, prolonged the duration of sleep induced by ethanol, and also enhanced ethanol-induced hypotermia ⁽¹⁵⁾. These results suggest that those neuropeptides may be involved in the complex mechanisms of action of ethanol on the CNS, and this participation can be mediated by the modifications in the activity of their degradative enzymes.

Discussion Board

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[ABSTRACT] [INTRODUCTION] [MATERIAL & METHODS] [RESULTS] [IMAGES] [DISCUSSION AND CONCLUSIONS] [BIBLIOGRAPHY] [Discussion Board]

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	[Endocrinology]	[Neuroscience]	[Pharmacology]	[Physiology]	[Toxicology]

María Dolores Mayas-Torres, José Manuel Martínez-Martos, María Jesús Ramírez-Expósito, María Jesús García-López, Isabel Prieto-Gómez, Garbiñe Arechaga-Maza, Manuel Ramírez-Sánchez
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Last update: 11/01/00