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A H Mulder

Publications and source records attributed to A H Mulder.

At least 199 records · Page 11Linked to original sources
PubMed1979

Presynaptic noradrenergic alpha-receptors and modulation of 3H-noradrenaline release from rat brain synaptosomes.

The depolarization (15 mM K+)-induced release of 3H-NA from superfused rat brain synaptosomes and the effects of alpha-noradrenergic drugs thereon were studied. Noradrenaline (NA; in the presence of the uptake inhibitor desipramine) reduced synaptosomal 3H-NA release. Reduction of the concentration of calcium ions in the medium during K+ stimulation greatly enhanced the sensitivity of 3H-NA release to alpha-receptor-mediated inhibition. Under these conditions NA dose-dependently inhibited 3H-NA release from synaptosomes obtained from cortex or hypothalamus, but did not affect 3H-NA release from striatal (i.e dopaminergic) synaptosomes. Adrenaline, clonidine and oxymetazoline potently inhibited 3H-NA release from cortex synaptosomes at concentrations in the nanomolar range. Phentolamine by itself did not affect synaptosomal 3H-NA release, but antagonized the inhibitory effects of both noradrenaline and adrenaline. The data obtained further substantiate the hypothesis that the alpha-receptors mediating a local negative feedback control of NA release are localized on the varicosities of central noradrenergic neurons, Furthermore, noradrenergic nerve terminals in the hypothalamus appear to be less senstive to alpha-receptor-mediated presynaptic inhibition than those in the cortex.

Adrenergic alpha-Agonists↗
PubMed1979

Identification of MSH release-inhibiting elements in the neurointermediate lobe of the rat.

Neurointermediate lobes of rats comprise elements which, when excited in vitro, bring about an inhibition of the release of melanocyte stimulating hormone (MSH). Superfusion of neurointermediate lobes of intact donor rats with medium containing 45 mM K+ induced a stimulation of the release of oxytocin, arginine-vasopressin and dopamine (DA) and inhibited the release of MSH. Fluorescence histochemical observations and the results of release studies indicate that electrothermic lesions in the mediobasal hypothalamus induced a more rapid degeneration of dopaminergic than of peptidergic terminals in the neurointermediate lobe. Dopaminergic nerve terminals and the stimulated release of DA had vanished completely on the second day after these lesions, which coincided with the disappearance of K+-induced inhibition of MSH release. Frontal hypothalamic deafferentations resulted in disappearance of peptidergic nerve terminals as evidenced by the development of diabetes insipidus and the strong decline of depolarization-induced release of oxytocin and vasopressin from neurointermediate lobes in vitro. In contrast, the dopaminergic plexus was left intact, as was the K+-induced stimulation of DA release and inhibition of MSH release. We conclude that the K+-induced inhibition of MSH release is mediated by DA rather than by neuropeptides from terminals in the neurointermediate lobe. The results are in agreement with the proposed MSH release-inhibiting role of the dopaminergic tuberoinfundibular neurones.

Afferent Pathways↗
PubMed1979

GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices.

The effects of GABA on depolarization-induced (26 mM K+) release of radiolabeled dopamine (DA) and acetylcholine (ACh) from slices of rat caudate nucleus were examined with a superfusion method. GABA, in concentrations of 10(-5)--10(-3) M, dose-dependently enhanced the release of DA, either accumulated by high-affinity uptake or synthesized from 14-C-tyrosine. In contrast, the release of ACh was reduced by GABA. This reduction appeared to be caused by the increase in DA-release. These effects of GABA decreased from the caudal to rostral part within the caudate nucleus, an order which parallels the distribution of endogenous GABA and glutamic acid decarboxylase. However, GABA had little, if any, effect in the nucleus accumbens. Since it was difficult to antagonize the effects of GABA on DA and ACh release with bicuculline or picrotoxin, it remains uncertain whether these effects were mediated via GABA receptors. In view of the high endogenous GABA level in the caudate nucleus it is concluded that GABA may be one of the local factors involved in the control of the amount of transmitter that will be released from dopaminergic varicosities upon depolarization.

Acetylcholine↗
PubMed1978

Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex.

The effects of adenosine and some related purines on the K+-induced release of 3H-noradrenaline from rat cerebral cortex slices were determined in a superfusion system. Adenosine and ATP caused a dose-dependent inhibition of 3H-NA release with a maximal effect of 35% at 10(-4) M. Theophylline, 10(-4) M, antagonized the inhibitory effect of adenosine. The results support the hypothesis that at least some of the central stimulant effects of the methylxanthines could be related to blockade of a purinergic inhibitory tone on noradrenergic synaptic output.

Adenosine↗
PubMed1978

Alpha-receptor-mediated modulation of 3H-noradrenaline release from rat brain cortex synaptosomes.

The effects of oxymetazoline and noradrenaline (in the presence of desipramine) on the release of 3H-noradrenaline from rat brain cortex synaptosomes were studied using a superfusion technique. Both drugs (at 1 micrometer concentrations) were found to reduce the depolarization-induced (15 mM K+) release of 3H-noradrenaline. The release-modulating effect of noradrenaline was antagonized by phentolamine and yohimbine. The data provide direct evidence for the hypothesis that alpha-receptors modulating the release of noradrenaline are localized on varicosities of central noradrenergic neurones.

Animals↗
PubMed1978

Facile syntheses of potent dopaminergic argonists and their effect on neurotransmitter release.

The facile syntheses of important intermediates used in the preparation of the two potent dopaminergic argonists, 2-amino-6,7-dihydroxytetrahydronaphthalene (11) (referred to by some authors as ADTN) and its 5,6-dihydroxyl isomer 12, are described. Thus 6,7-dimethyoxy-2-tetralone has been prepared in two steps and 5,6-dimethoxy-2-tetralone in three steps both from commercially available materials. The effects of 11, 12, and the noncatechol analogue, 2-aminotetrahydronaphthalene (ATN), on radioactive neurotransmitter release have been studied in vitro using rat brain slices. It has been shown that both 11 and 12, at a concentraiton of 2 micron, cause a release of [3H]-DA and NA, 11 being more potent than 12 in releasing [3H]-DA. ATN (2 micron) was found to be inactive in these experiments which shows the importance of the catechol function in this uptake--release process.

Adrenergic Agonists↗
PubMed1977

Increased dopamine release from rat striatal slices by inhibitors of GABA-aminotransferase.

The effects were examined of two inhibitors of GABA-aminotransferase, amino-oxyacetic acid (AOAA) and RMI-71645-16, on depolarization-induced (30 mM K+) dopamine (DA) release from rat striatal slices. When added to the medium, these drugs increased the release of radiolabeled DA, either accumulated by high-affinity uptake or synthesized from 14C-tyrosine. AOAA did not modify the release of 14C-acetylcholine from striatal slices or 3H-noradrenaline from cortical slices. Moreover, 3H-DA release from substantia nigra was not affected. The data suggest the possibility that the effects of GABA-T inhibitors on striatal DA release are mediated by intrinsic GABA-ergic neurons.

4-Aminobutyrate Transaminase↗
PubMed1977

Modulation by histamine of the efflux of radiolabeled catecholamines from rat brain slices.

Histamine induced a dose-dependent stimulation of 3H-catecholamine(CA) efflux (superfusion procedure) from hypothalamic, striatal, hippocampal and cortical slices. The extra-hypothalamic regions were the most sensitive to histamine. Efflux of 14C-GABA and 14C-(acetyl)choline was not affected. The effect of histamine on 3H-CA efflux developed slowly, reaching its maximum after 15-20 min. Histamine was inefffective with tissue from reserpinized animals. The major part of the radioactivity released by histamine consisted of CA metabolites. Histamine apparently does not enter catecholaminergic neurons, since tyramine and the CA had no effect on the efflux of 3H-histamine previously taken up by brain slices. After incubation of slices with 3H-CA in the presence of histamine and subsequent superfusion, tyramine or K+ -depolarization induced much less 3H-CA release than from control slices not incubated with histamine. It is suggested that histamine may act as a modulator of presynaptic catecholaminergic processes in the central nervous system by causing a depletion of the transmitter stores in the nerve terminals.

Acetylcholine↗
PubMed1977

Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum.

The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS.

Animals↗
PubMed1976

Cyclic AMP and alpha-receptor-mediated modulation of noradrenaling release from rat brain slices.

Oxymetazoline (an alpha-receptor agonist) reduced and phentolamine (an alpha-receptor antagonist) increased depolarization-induced release (potassium or electrical field stimulation) of 3H-noradrenaline (NA) from superfused neocortical slices in a dose-dependent way. Inhibition of phosphodiesterase also reduced NA release; this effect could be reversed by phentolamine. Phosphodiesterase inhibition potentiated the effect of oxymetazoline. It is suggested that stimulation of presynaptic alpha-receptors may reduce NA release up to about 60% and that increased cyclic AMP formation might be involved in this modulation.

Animals↗