Age-related changes in neuronal uptake of noradrenaline.
Age-related changes in the neuronal uptake of noradrenaline were studied in the vas deferens of 4-, 12- and 20-months old rats by determining the potentiating effect of cocaine on concentration-effect curves to noradrenaline and by evaluating the kinetic parameters (Vmax and apparent Km) of neuronal 3H-noradrenaline uptake. Since the neurotransmitters released by nerve terminals and the density of noradrenergic innervation are different in the epididymal and prostatic portion of the vas, the experiments were carried out in these two portions of the organ. In the epididymal portion, the ratio between EC50 for noradrenaline in the presence and in the absence of cocaine was reduced in tissues of middle-aged (12-months) and old (20-months) animals when compared with young (4-months) animals. The pD2 values for noradrenaline in the absence of cocaine and the kinetic parameters for neuronal 3H-noradrenaline uptake were not modified by ageing. Thus, in the epididymal portion there was no age-related change in neuronal uptake. The age-related decrease in the cocaine-induced supersensitivity to noradrenaline was due to an age-related decrease in the pD2 value for noradrenaline observed in the presence of cocaine, suggesting postsynaptic changes. In the prostatic portion, the ratio between EC50 for noradrenaline in the presence and in the absence of cocaine was also reduced in tissues of old animals (20-months) when compared with middle-aged and young animals. The pD2 value for noradrenaline in the absence of cocaine obtained in the prostatic portion of 20-months old rats was higher than that in the younger groups (4- and 12-months).(ABSTRACT TRUNCATED AT 250 WORDS)
de Avellar
M C
MC
Departamento de Farmacologia, Escola Paulista de Medicina, São Paulo, Brasil.
Kobashi
Y L
YL
Markus
R P
RP
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000294:innervation / Q000378:metabolism
D009419:Nerve Tissue Proteins; D003042:Cocaine; D009638:Norepinephrine