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Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 595 records · Page 33Linked to original sources
PubMed1975

The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol.

Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired.

Adenylyl Cyclases↗
PubMed1975

Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action diazepam.

Subcutaneous injections of isoniazid or picrotoxin increase the cerebellar content of 3',5'-cyclic guanosine monophosphate (cGMP) without changing the 3',5'-cyclic adenosine monophosphate cAMP. This increase was dose dependent and the threshold for the cGMP increase was lower than that for convulsions. In cerebellum the increase of cGMP content elicited by isoniazid but not that caused by picrotoxin was paralleled by a decrease of GABA content. Diazepam doses starting from 1.74 mumol/kg intraperitoneally produced a dose dependent decrease of cerebellar cGMP concentration without changing cAMP or GABA content. Smaller doses of diazepam (0.5 mumol/kg i.p.)failed to decrease the basal cerebellar content of cGMP. However, this dose of diazepam antagonized the increase of cGMP produced by isoniazid but not that produced by picrotoxin. Higher doses of diazepam were necessary to block the increase of cerebellar cGMP elicited by picrotoxin. Low doses of diazepam (0.14 mumol/kg) antagonized the convulsions in 50% of the rats injected with 3.3 mmol/kg of isoniazid. The doses of diazepam required to block picrotoxin, pentylenetetrazol or strychnine convulsions were 7, 25 and 40 times higher than those required to block isoniazid convulsions, respectively. Desmethyldiazepam, chloridiazepoxide, oxazepam were also several times more potent in antagonizing isoniazid than picrotoxin, pentylenetetrazol, or strychnine convulsions. In contrast, barbiturates were equipotent against all the convulsants studied. These experiments suggest that diazepam may act in the CNS either by altering the disposition of endogenous GABA or by mimicking the action of GABA at specific synaptic receptors.

Aminobutyrates↗
PubMed1975

Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.

An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 mumol/kg intraperitoneally) or reserpine and propranolol (40 mumol/kg intraperitoneally 30 min before reserpine), or exposed to 4 degrees for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme;the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process.

Adrenal Medulla↗
PubMed1975

Application of principles of steady-state kinetics to the in vivo estimation of acetylcholine turnover rate in mouse brain.

The rate of metabolism of acetylcholine (ACh) in mouse brain in vivo has been estimated utilizing a radio gas chromatographic approach and pulse labeling with radioactive phosphorylcholine. A kinetic model describing the change with time of the plasma choline (Ch), brain Ch and ACh specific radioactivities as interdependent variables is postulated. The experimental results are analyzed kinetically according to this model using two methods: the finite difference method described by Neff et al. (J. Pharmacol. Exp. Ther. 176: 701-710, 1971) and a simple graphic method based on the transformation of the data in terms of the decline of plasma Ch radioactivity described in this paper. The accuracy of the latter is evaluated by the classic method of the least mean squares. Calculations with the two methods yield comparable results. This method is simple and can be used to study drug effects on brain ACh turnover rate. ACh turnover rate in mouse brain has been calculated to be 0.36 mumol/g/hr with the latter method, whereas the finite difference method yields slightly lower values. Because of the compartmentalization of brain Ch and the inherent assumptions, the new method can be used only for data collected during the exponential decline of plasma radioactive choline.

Acetylcholine↗
PubMed1975

Application of principles of steady-state kinetics to the estimation of brain acetylcholine turnover rate: effects of oxotremorine and physostigmine.

We have measured the turnover rate of acetylcholine (ACh) in the brains of mice injected with doses of oxotremorine and physostigmine that cause a prolonged increase of ACh concentration in brain. The method used to measure turnover rate of ACh is an application of principles of steady-state kinetics to the change with time of brain choline (Ch) and ACh specific radioactivities after an intravenous pulse injection of phosphorylcholine. We have found that when the concentration of brain ACh and Ch is increased to a new steady state as a result of oxotremorine and physostigmine injections the turnover rate of brain ACh decreases from 0.34 mumol/g/hr (in saline-treated mice) to 0.12 and 0.061 mumol/g/hr, respectively. The possibility that an increase of brain Ch or ACh concentrations plays a role in the control of brain ACh turnover rate is discussed.

Acetylcholine↗
PubMed1975

Morphine dependence and in vivo turnover of acetylcholine in whole mouse brain.

Turnover rates of acetylcholine (ACh) were estimated in mouse brain after intravenous injection of phosphoryl(Me-14C)choline by applying principles of steady-state kinetics to the change with time of choline and ACh specific radioactivities. Turnover rate of brain ACh was estimated: 1) 45 minutes after a single injection of morphine (350 mumol/kg); 2) 3.5 days after implantation of a morphine pellet (250 mumol/pellet); 3) 15 minutes after 24 mumol/kg of naloxone to precipitate withdrawal in mice implanted with morphine pellets for 3.5 days; and 4) 15 minutes after 24 mumol/kg of naloxone. Brain ACh turnover rate was unchanged in mice that were given a single injection of morphine but was increased significantly in mice that had been made physically dependent upon morphine. During naloxone-precipitated withdrawal, the brain ACh turnover rate was found to be equal to that of mice treated only with naloxone.

Acetylcholine↗