Age-related changes in neuronal uptake of noradrenaline

Summary 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 (V_max and apparent K_m) 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 beween 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). Since in the presence of cocaine no age-related changes in the pD₂ value for noradrenaline were obtained, postsynaptic changes might not occur in this portion. Thus, the reduction in the EC₅₀ ratio for noradrenaline in the prostatic portion of 20-months old rats suggested a loss of function of the neuronal uptake system. Further support for this hypothesis was that the V_max value of neuronal ³H-noradrenaline uptake tended to decline with age only in the prostatic portion.Therefore, the age-related decrease in the cocaine-induced supersensitivity was probably due to an age-related loss of function of the neuronal uptake system in the prostatic portion and to a decrease in the sensitivity to noradrenaline in the epididymal portion. The loss of function of neuronal uptake and the change in sensitivity to noradrenaline occurred at different ages.Part of the present results have been reported in the III Annual Meeting of the Federação de Sociedades de Biologia Experimental, Caxambu, MG, June 29 — July 3, 1988Send offprint requests to R. P. Markus, Departamento de Farmacologia, Instituto de Ciencias Bimédicas, Universidade de São Paulo, Av. Prof. Linen Prestes, 1524, 05508, Sao Paulo, Brasil