Effects of pentoxifylline and theophylline on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus

Abstract Preincubation of synaptosome-rich homogenates of rat hypothalamus with pentoxifylline [3,7-dimethyl-1(5-oxo-hexyl)-xanthine] or theophylline resulted in significant decreases of norepinephrine, dopamine, serotonin and glutamate uptake. Methylxanthine inhibition was non-competitive; apparent Ki's ± S.E.M. for pentoxifylline and theophylline were 0.48 ± 0.03 and 0.84 ± 0.10 mM (norepinephrine), 0.20 ± 0.02 and 0.35 ± 0.05 mM (dopamine), 0.22 ± 0.03 and 0.98 ± 0.12 mM (serotonin) and 0.69 ± 0.08 and 1.13 ± 0.14 mM (glutamate). Methylxanthines did not affect the synaptosomal uptake of leucine, phenylalanine or alanine. Transmitter release evoked by increasing [K+] in the medium was augmented by pentoxifylline and theophylline in a dose-dependent manner. Dibutyryl cyclic AMP (1.0 mM) caused a significant increase of transmitter release following elevation of [K + ] in the medium but did not affect neurotransmitter uptake by hypothalamic synaptosomes.

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