[Aminoglycoside antibiotics neomycin and kanamycin inhibit the increase of of pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of the frontal cortex of the rate].
BACKGROUND
Thyrotrophin releasing hormone (TRH) has emerging in the last few years as a neuropeptide with important functions, not only as neurohormone into the hypothalamus-pituitary axis, but as neurotransmitter in several areas of the nervous system. Although little is known about its extra-endocrine functions, TRH has been related with several types of psychiatric disorders. Pyroglutamyl aminopeptidase (pGluAP) is the enzyme involved in the degradation of TRH.


OBJECTIVE
The present research studies the levels of pGluAP activity under basal (resting) and KCl-stimulated (depolarized) conditions. The role of intracellular free calcium homeostasis, by means of the aminoglycoside antibiotics neomycin and kanamycin as voltage-dependent calcium channels blockers, is also studied.


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 KCl-stimulated (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 4,5-bisphosphate breakdown products is also suggested.
Ramírez-Expósito
M J
MJ
Area de Fisiología, Facultad de Ciencias Experimentales y de la Salud, Universidad de Jaén, España. mramirez@ujaen.es
Martínez-Martos
J M
JM
Mayas
M D
MD
Tsuboyama
G
G
Prieto
I
I
Arechaga
G
G
Ramírez
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects*; D007612:Kanamycin / Q000494:pharmacology*; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D011751:Pyroglutamyl-Peptidase I / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000187:drug effects
D000900:Anti-Bacterial Agents; D015220:Calcium Channels; D007612:Kanamycin; D013973:Thyrotropin-Releasing Hormone; D011751:Pyroglutamyl-Peptidase I; D009355:Neomycin