RESUMEN
The effect of chronic (8-week long) 5 percent-ethanol consumption on the activity of tyrosine hydroxylase on the rat brain hypothalamus, striatum and midbrain was studied. In rats with strong ethanol prefence the enzyme activity was found to increase by 65-86 percent in the hypothalamus and to diminish by 52-68 percent and 29-68 percent in the midbrain and striatum, respectively. In rats with weak ethanol preference the enzyme activity in the brain striatum and midbrain remained unchanged, while in the hypothalamus it decreased by 25-40 percent. Chronic ethanol consumption had no effect on the inhibition of the enzyme activity neither by dopamine (8.0 X10(-4)M), nor tyrosine (in an inhibitory concentration of 3.7X(10(-4)M).
Asunto(s)
Encéfalo/enzimología , Etanol/farmacología , Oxigenasas de Función Mixta/metabolismo , Animales , Encéfalo/efectos de los fármacos , Cuerpo Estriado/enzimología , Dopamina/farmacología , Activación Enzimática/efectos de los fármacos , Hipotálamo/enzimología , Masculino , Mesencéfalo/enzimología , Oxigenasas de Función Mixta/antagonistas & inhibidores , Ratas , Tiroxina/farmacología , Factores de TiempoRESUMEN
The effect of electrical stimulation on the membrane-bound tyrosine hydroxylasectivity of the rat hypothalamus synaptosomes was studied. The electrical stimulation caused an elevation of O2 consumption and the elevation of glycolysis indicating synaptosome excitation. The membrane-bound tyrosine hydroxylase activity increased under these conditions. The KM value for tyrosine decreased from 0.091 to 0.026 mM. Noradrenaline inhibition of the enzymatic activity diminished. It is assumed that the effect of depolarization on the catecholamine synthesis velocity in the nerve endings involves tyrosine hydroxylase modification.
Asunto(s)
Hipotálamo/enzimología , Sinaptosomas/enzimología , Tirosina 3-Monooxigenasa/metabolismo , Animales , Estimulación Eléctrica , Glucólisis , Hipotálamo/metabolismo , Hipotálamo/ultraestructura , Cinética , Masculino , Norepinefrina/farmacología , Consumo de Oxígeno , RatasRESUMEN
The influence of cocaine on tyrosine hydroxilase of rat brain hypothalamus was investigated in vivo (0.5 mg/kg) and in vitro (10(--6)--10(--5)M). Cocaine was used as a substance with a known adrenergic type of action. It was shown that under standard conditions cocaine in vitro increased the enzyme activity and decreased the Km for DMPH4 cofactor without changing Vmax of the reaction analyzed by the membrane enzyme. Cocaine in vitro decreased the tyrosine hydroxylase activity, especially that of the membrane enzyme. In this case there occurred a decrease of Km for DMPH4 and a decrease of Vmax of the reaction. The decrease of Vmax is considered to be the result of the secondary effect of cocaine.
Asunto(s)
Cocaína/farmacología , Hipotálamo/enzimología , Tirosina 3-Monooxigenasa/metabolismo , Animales , Masculino , Membranas/enzimología , Ratas , SolubilidadRESUMEN
A rate of the tyrosine hydroxylase reaction was estimated by an increase in absorption at 335 nm, which was caused by oxidation of pterin cofactor 6,7-dimethyl-5, 6, 7, 8-tetrahydroxypterin (DMPH) coupled with the convertion of the substrate 1-tyrosine into dihydroxyphenylalanine. At pH 6.2 the ratios of molar extinction were as follows: in trisacetate ADMPH4-1370, ADMPH2-5350; in tris-malate tadmph4-1250, admph25300. the enzyme, associated with membranes, had the Km value for Tyr-0.045 mM, the Km for DMPH4 was 0.18 mM; the soluble enzyme had Km for Tyr-0,050 mM, the Km for DMPH4 was 0.74 mM. The stoichiometry of the reaction was 1:1 (I mole DOPA per I mole of DMPH2 formed).
Asunto(s)
Espectrofotometría/métodos , Tirosina 3-Monooxigenasa/análisis , Absorción , Relación Dosis-Respuesta a Droga , Concentración de Iones de Hidrógeno , Punto Isoeléctrico , Cinética , Oxidación-Reducción , Pterinas/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
A study was made of the effect of a number of neuroleptics of various chemical structure of tyrosine-hydroxilase isolated from the synaptosomes of rat hypothalamus. A direct spectrophotometric method of determination of the activity of the enzyme was used; it was based on measurement of the absorbence at 335 nm (at the isobestic point for oxidized forms of a synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydropterine). At the tyrosine concentration of 0.15 muM haloperidol, haloanizon, and fluorophenazin were found to increase, and triperidol, droperidol and carbidin -- to decrease the initial rate of thyrosinehydroxilase reaction. All the neuroleptics under study proved to be capable of eliminating the substrate inhibition of the enzyme occurring with a rise of tyrosine concentration to 0.3 mM. The KM value for tyrosine failed to alter with the action of neuroleptics. The effect of neuroleptics was assumed to be of allosteric nature.