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Biomedical subjects

J O Schenk

Publications and source records attributed to J O Schenk.

27 records · Page 2Linked to original sources
PubMed1992

Blockade of dopamine autoreceptors by haloperidol and the apparent dynamics of potassium-stimulated endogenous release of dopamine from and reuptake into striatal suspensions in the rat.

A study was made to determine what effects the blockade of dopamine (DA) autoreceptors has on the dynamics of depolarization-stimulated release of DA from suspensions of the striatum. A rotating disk electrode voltammetric technique and a first order kinetic model were used to measure and quantify time-resolved depolarization-induced release of DA from and reuptake into the same striatal suspension. Multiphasic dose-response relationships between the magnitudes, rates and apparent rate constants of release of DA and the concentration of the autoreceptor antagonist, haloperidol, were observed. At small concentrations of haloperidol, less than or equal to 0.1 microM, the magnitude of release of DA and apparent release rate constants were increased, however, the duration of release, the initial rate of release and the rate constants of reuptake of DA were unaffected. At larger concentrations of haloperidol, greater than 1.0 microM, release of DA was prolonged and reuptake was decreased. The rate constants for release of DA correlated with the magnitude of release of DA at all of the concentrations of haloperidol studied. The concentrations of haloperidol in tissue were estimated and then correlated with functionally significant systemic doses of haloperidol by direct comparison to published data, relating total concentrations of haloperidol in tissue with systemic doses and their behavioral effects. At these doses, haloperidol was found to increase the release rate constant and magnitude of release of DA, without altering the duration of release or the timing of reuptake. Thus, at presumed functionally significant doses, autoreceptor antagonism resulted in a modulation of the amplitude of release of DA only.

Animals↗
PubMed1991

Effects of acute and chronic systemic administration of some typical antipsychotic drugs on turnover of dopamine and potassium ion-induced release of dopamine in the striatum of the rat in vivo.

Chronoamperometry was used to measure the dose dependency of antipsychotic drug (spiperone, haloperidol and chlorpromazine)-induced increases in depolarization-stimulated release of dopamine in the striatum of the rat in vivo. The dose-response curves were found to be at least biphasic (small doses increased release and large doses inhibited release) and different in shape from dose-response curves for increases in the turnover of dopamine, suggesting that the two processes may not be related. The threshold dose to induce increased depolarization-stimulated release of dopamine correlated with the values in the literature for doses required to block stereotype induced by apomorphine and amphetamine and doses sufficient to cause a maximal increase in release correlated with the doses required for the induction of catalepsy. In addition, the ratio of the doses required to obtain half-maximal and maximal increases in stimulated release of dopamine, matched values in the literature of the ratio of doses required to ameliorate psychotic symptoms, whereas the doses required to reverse the increase induced by antipsychotic drugs did not. Chronic administration of haloperidol resulted in alterations in the dose-response curves for both the release and turnover of DA. Chronic administration caused a reversal of the effect of acute administration in the small dose range (inhibition as opposed to enhancement of release), a decrease in the maximum magnitude of release of dopamine obtained and an overall shift to the right of the dose-response curve. Chronic administration of haloperidol decreased turnover, relative to animals receiving the drug acutely and no shift in the position of the dose-response curve was observed.

Animals↗
PubMed1991

Interactions between the argininyl moieties of neurotensin and the catechol protons of dopamine.

The interaction between dopamine and neurotensin as well as other Arg-containing peptides was studied to provide more chemical details of how dopamine binds to the neuropeptide neurotensin. The stoichiometry of 1:1, dopamine to neurotensin, was confirmed by additional electroanalytical and ultraviolet-visible spectroscopic studies. By analyses of the 205- to 340-nm difference spectra of fixed concentrations of dopamine in the presence of increasing amounts of neurotensin, the dissociation constant of the interaction was found to be 5.9 x 10(-8) mol/L. This finding confirmed (by a second physical method) the previously reported KD value obtained by electroanalytical techniques. The associations between dopamine and neurotensin as well as the neurotensin fragment Pro7-Arg8-Arg9-Pro10 were found to be pH dependent when the dissociation constant was measured as a function of pH (in 150 mmol/L NaCl). The results of studies of the formal potential of dopamine in the presence of Arg and Arg-containing peptides confirmed that catechol protons are directly involved in the association and that the chemical species of dopamine associated with neurotensin is a catecholate form. The (pseudo)-first-order rate constant of dissociation of the complex at pH 7.6, measured by the chronoamperometric and rotating disk electroanalytical techniques, was found to be approximately 10(5) s-1, indicating that the rate of formation of the complex is under diffusion control. A hypothetical chemical structure of the neurotensin-dopamine complex is suggested.

Amino Acid Sequence↗
PubMed1990

Neurotensin binding to dopamine.

Rotating disk electrode voltammetry at glassy carbon electrodes and ultraviolet/visible spectroscopy were used to demonstrate that dopamine binds to neurotensin with a dissociation constant of 7.5 x 10(-8). By measuring the binding constants of various neurotensin analogs, it was found that the -Arg8-Arg9-portion of the neurotensin sequence is critical for binding dopamine. Neurotensin also formed a complex with 4-ethylcatechol, 4-methylcatechol, 3-methoxytyramine, and norepinephrine. Although changes in the side chain did not alter the binding constant, methoxylation of the catechol moiety significantly increased the dissociation constant. These data along with additional studies of dopamine interactions with arginine derivatives suggest that the guanidino groups of arginine and the catechol hydroxyls of dopamine are responsible for mediating the observed binding. It is hypothesized that the capacity of neurotensin to bind directly to dopamine may be partly responsible for its previously observed antagonism of dopamine-induced locomotor activity.

Dopamine↗
PubMed1987

Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia.

Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms.

Animals↗
PubMed1983

Chronoamperometry in brain slices: quantitative evaluations of in vivo electrochemistry.

Practical utilization of in vivo electrochemistry for brain studies has been impeded by difficulties with specificity and quantitative measurements. Studies in brain slices combined with similar data from intact animals have provided important new information on the nature of the electrochemical studies. Using the enzyme ascorbic acid oxidase (AAO), the primary signal contribution has been calculated to come from ascorbic acid. By inhibiting monoamine oxidase activity with pargyline, the second most important contributor in caudate extracellular fluid is postulated to be 3,4-dihydroxyphenylacetic acid. These species are calculated to constitute over 93% of the observed oxidation current in rat caudate extracellular fluid.

3,4-Dihydroxyphenylacetic Acid↗