RESUMEN
The content of cyclic AMP (cAMP) in the slices of rat striatum and cerebral cortex was tested after incubation with various concentrations (10(-6)--10(4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), and dimethylaminoadamatane (DMAD), and incubation with DA, AMD and DMAD in combination with KCl (43 mM) or haloperidol (HP) (10(-5) M). APM, AMD, and DMAD act synergistically with DA, elevate the c-AMP content in the striatum less than DA dose and do not affect the level c-AMP in the slices of cerebral cortex. KCl potentiated the action of DA, but inhibited that of APM, AMD, and DMAD. HP was most effective in blocking the action of DA, and blocked more weakly the action of APM AMD, DMAD, and the action of DA, APM, AMD, and DMAD in the presence of high concentration of KCl. The results indicate that APM, AMD, and DMAD, are less specific stimulants of central dopaminergic structures than DA, and that the increase of c-AMP content in the slices of rat striatum caused by APM, AMD, and DMAD is due to depolarizing action of these compounds.
Asunto(s)
Amantadina/análogos & derivados , Amantadina/farmacología , Apomorfina/farmacología , Cuerpo Estriado/metabolismo , AMP Cíclico/metabolismo , Memantina/farmacología , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , Dopamina/farmacología , Interacciones Farmacológicas , Haloperidol/farmacología , Técnicas In Vitro , Masculino , Cloruro de Potasio/farmacología , Ratas , Factores de TiempoRESUMEN
Two forms of phosphodiesterase exist in the rat striatum, one with high (PDE -- I), and one with low (PDE -- II) affinity to substrate (cyclic 3',5'-AMP). The results obtained suggest that inhibition of PDE -- I activity by apomorphine or amantadine is partially related to their stimulating effect on dopaminergic system in the striatum.
Asunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Cuerpo Estriado/enzimología , Dopamina/fisiología , Hidrolasas Diéster Fosfóricas/metabolismo , Amantadina/farmacología , Anfetamina/farmacología , Animales , Apomorfina/farmacología , Cuerpo Estriado/efectos de los fármacos , Dopamina/farmacología , Técnicas In Vitro , Cinética , Masculino , Ratas , Estimulación QuímicaRESUMEN
The neurotransmitter catecholamines control metabolism 5-HT in pineal gland by stimulating pineal serotonin-N-acetyltransferase (EC 2.3.1.5) activity [1, 2]. To prove the influence of FP on the metabolism 5-HT provoked by norepinephrine was tested. Rat pineal gland were incubated in media containing 5-HT- 14C or 5-HT- 14C and FP (1-10(-6)-1-10(-4) M). Norepinephrine (1-10(-6)-1-10(-4)M) was added at the start of the experiment. The level of cyclic 3',5'-AMP, activity of HIOMT and metabolites of 5-HT-14C was examined. The results have suggested that the FP inhibit the provoked by norepinephrine metabolism of 5-HT in the rat pineal gland by decrease the formation of c-3',5'-AMP.