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Depolarization increases pyroglutamyl aminopeptidase activity in rat frontal cortex synaptosomes. inhibitory effect of aminoglycoside antibiotics neomycin and kanamycin
Introduction. Thyrotrophin releasing hormone (TRH) has emerging in the last few years as a neuropeptide with important functions, not only as neurohormone into the hypothalamuspituitary axis, but as neurotransmitter in several areas of the nervous system. Although little is known about its extraendocrine functions, TRH has been related with several types of psychiatric disorders. Pyroglutamyl aminopeptidase (pGluAP) is the enzyme involved in the degradation of TRH. Objectives. The present research studies the levels of pGluAP activity under basal (resting) and KClstimulated (depolarized) conditions. The role of intracellular free calcium homeostasis, by means of the aminoglycoside antibiotics neomycin and kanamycin as voltagedependent calcium channels blockers, is also studied. Material and methods. Both pGluAP activity and intracellular free calcium concentration were analyzed in synaptosomes obtained from the frontal cortex of rats. Synaptosomes were incubated in artificial cerebrospinal fluid, under basal (resting) or KClstimulated (depolarized) conditions, with of without neomycin or kanamycin at different concentrations. Results. Depolarization increases significantly pGluAP activity, which is completely abolished by neomycin and kanamycin at the lower concentrations used. On the contrary, aminoglycoside antibiotics do not block completely the increase on intracellular free calcium concentration induced by depolarization. Under basal conditions, no changes were found on pGluAP activity nor intracellular free calcium. Conclusions. pGluAP activity could regulate the neurotransmitter/neuromodulatory functions of TRH trough intracellular free calcium movements through aminoglycoside-sensitive voltage-dependent calcium channels. A role for inositol 4,5bisphosphate breakdown products is also suggested.
AminoglycosidesCalcium channelsDepolarizationFrontal cortexKanamycinNeomycinPyroglutamyl aminopeptidaseSynaptosomesThyrotrophin releasing hormone