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At least 523 records · Page 29Linked to original sources
PubMed1992

Melatonin increases serotonin N-acetyltransferase activity and decreases dopamine synthesis in light-exposed chick retina: in vivo evidence supporting melatonin-dopamine interaction in retina.

The administration of melatonin, either peripherally (0.01-10 mg/kg) or intraocularly (0.001-10 mumol/eye), to light-exposed chicks dose-dependently increased serotonin N-acetyltransferase (NAT) activity in retina but not in pineal gland. The effect of melatonin was slightly but significantly reduced by luzindole (2-benzyl-N-acetyltryptamine), and not affected by two other purported melatonin antagonists, N-acetyltryptamine and N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23). The elevation of the enzyme activity induced by melatonin was substantially stronger than that evoked by 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, or 5-methoxytryptamine. The melatonin-evoked rise in the retinal NAT activity was counteracted by two dopamine D2 receptor agonists, quinpirole and apomorphine, and prevented by the dopamine D2 receptor blocker spiroperidol, and by an inhibitor of dopamine synthesis, alpha-methyl-p-tyrosine. Melatonin (0.1-10 mg/kg i.p.) dose-dependently decreased the levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), as well as the DOPAC/dopamine ratio, in chick retina but not in forebrain. The results obtained (1) indicate that melatonin in vivo potently inhibits dopamine synthesis selectively in retina, and (2) suggest that the increase in retinal NAT activity evoked by melatonin in light-exposed chicks is an indirect action of the compound, and results from the disinhibition of the NAT induction process from the dopaminergic (inhibitory) signal. The results provide in vivo evidence supporting the idea (derived on the basis of in vitro findings) that a mutually antagonistic interaction between melatonin and dopamine operates in retinas of living animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Investigations about a direct neurotensin-dopamine interaction by nuclear magnetic resonance study, synaptosomal uptake of dopamine, and binding of neurotensin to its receptors.

Interactions between dopamine and neurotensin can occur at various levels of the dopaminergic pathways. By using different approaches in vitro, we investigated the proposed hypothesis that neurotensin might bind to dopamine in the synaptic cleft. Nuclear magnetic resonance spectra of neurotensin were not modified by the addition of dopamine, and no nuclear Overhauser effect was detected. Synaptosomal uptake of [3H]dopamine in the presence of neurotensin did not lead to any modifications of the kinetic constants of the uptake. Neurotensin binding was not modified by the addition of dopamine. These results did not confirm the suggestion that neurotensin can form a complex with dopamine.

Animals↗
PubMed2005

Characterization of a novel D2-like dopamine receptor with a truncated splice variant and a D1-like dopamine receptor unique to invertebrates from Caenorhabditis elegans.

We have cloned two novel Caenorhabditis elegans dopamine receptors, DOP-3 and DOP-4. DOP-3 shows high sequence homology with other D2-like dopamine receptors. As a result of alternative splicing, a truncated splice variant of DOP-3, DOP-3nf, was produced. Because of the in-frame insertion of a stop codon in the third intracellular loop, DOP-3nf lacks the sixth and seventh transmembrane domains that are found in the full-length DOP-3 receptor. Reporter gene assay showed that DOP-3 attenuates forskolin-stimulated cAMP formation in response to dopamine stimulation, whereas DOP-3nf does not. When DOP-3 was coexpressed with DOP-3nf, the ability to inhibit forskolin-stimulated cAMP formation was reduced. DOP-4 shows high sequence homology with D1-like dopamine receptors unique to invertebrates, which are distinct from mammalian D1-like dopamine receptors. Reporter gene assay showed that DOP-4 stimulates cAMP accumulation in response to dopamine stimulation. These two receptors provide new opportunities to understand dopaminergic signaling at the molecular level.

Amino Acid Sequence↗
PubMed1982

Comparison of the vasodilator action of dopamine and dopamine agonists in the renal and coronary beds of the dog.

1 The effects of dopamine and the dopamine receptor agonists, SK&F 38393 and bromocriptine, on renal and coronary blood flow in the anaesthetized dog were examined. Dopamine was found to dilate both vascular beds, whereas SK&F 38393 increased renal blood flow but did not have any dilator activity in the coronary vasculature. Bromocriptine did not cause vasodilatation in either vascular bed. 2 The vasodilator responses to dopamine and SK&F 38393 were significantly reduced by the dopamine receptor antagonists, ergometrine or metoclopramide. 3 It is proposed that the selective action of SK&F 38393 on the renal vasculature suggests that the dopamine receptors of the renal and coronary vascular beds may be of different types.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Presynaptic dopamine receptors in the pithed rat: characterization with apomorphine and comparison with central dopamine autoreceptors.

Apomorphine, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 micrograms/kg intravenously) of the stimulation-induced increase in diastolic blood pressure in the pithed rat. This effect of apomorphine could be antagonized with (-)-sulpiride or haloperidol but not with yohimbine or atropine, indicating the involvement of inhibitory dopamine receptors. The alpha-1-adrenoceptor mediated pressor response to phenylephrine (5 micrograms/kg intravenously) was not significantly attenuated by apomorphine. The sensitivity of peripheral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorphine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynaptic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopamine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments.

Animals↗
PubMed1993

Prolactin stimulates [3H]dopamine release from dispersed rat tubero-infundibular dopaminergic neurons and dopamine decreases gonadotropin-releasing hormone release induced by calcium ionophore.

In order to investigate the involvement of prolactin-dopamine and dopamine-gonadotropin interactions in the hypothalamo-pituitary axis of hyperprolactinemia, in vitro studies were performed using primary cultures of dispersed rat hypothalamic heterogeneous cells containing tubero-infundibular dopaminergic neurons or gonadotropin-releasing hormone (GnRH) neurons. We observed that prolactin caused dose-dependent stimulation of [3H]dopamine release after a 16-h incubation. Staurosporin (10 nmol/l), an inhibitor of protein kinase C, significantly reduced the [3H]dopamine release induced by prolactin (1 mg/l). Incubation of tubero-infundibular dopaminergic neurons with prolactin (1 mg/l) had no effect on intracellular cyclic adenosine monophosphate accumulation. Dopamine (1 mumol/l) significantly (p < 0.01) reduced the release of GnRH induced by 50 mumol/l calcium ionophore from dispersed hypothalamic cells from the preoptic area, while prolactin had no effect on GnRH release. These data support the hypothesis that the antigonadotropic effect of prolactin on the hypothalamus is mediated by an inhibitory effect of dopamine on GnRH release.

Animals↗
PubMed2005

Tyrosine and tyramine increase endogenous ganglionic morphine and dopamine levels in vitro and in vivo: cyp2d6 and tyrosine hydroxylase modulation demonstrates a dopamine coupling.

BACKGROUND: The ability of animals to make morphine has been in question for the last 30 years. Studies have demonstrated that animals do contain morphine precursors and metabolites, as well as the ability to use some morphine precursors to make morphine. MATERIAL/METHODS: The present study uses excised ganglia from the marine invertebrate Mytilus edulis as well as whole animals. Morphine and dopamine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay. Tissues and whole animals were also exposed to morphine precursors and exposed to the CYP2D6 inhibitor quinidine and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Additionally, via RT-PCR, a cDNA fragment of the CYP2D6 enzyme in the ganglia of M. edulis was identified. RESULTS: Pedal ganglia incubated with either tyramine or tyrosine, or whole animals receiving injections, exhibited a statistically significant concentration- and time-dependent increase in their endogenous morphine and dopamine levels (2.51 +/- 0.76 ng/g for tyrosine and 2.39 +/- 0.64 ng/g for tyramine compared to approximately 1.0 ng/g morphine wet weight). Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process. We also demonstrated that CYP2D6 mediates the tyramine to dopamine step in this process, as did tyrosine hydroxylase in the step from tyrosine to L-DOPA. Furthermore, via RT-PCR, we identified a cDNA fragment of the CYP2D6 enzyme in the ganglia, which exhibits 94% sequence identity with its human counterpart. Evidence that tyrosine and tyramine were, in part, being converted to dopamine then morphine, and that this process can be inhibited by altering either or both CYP2D6 or tyrosine hydroxylase, is also provided. CONCLUSIONS: It appears that animals have the ability to make morphine. This process also appears to be dynamic in that the inhibition of one pathway allows the other to continue with morphine synthesis. Moreover, dopamine and morphine synthesis were coupled.

Animals↗
PubMed1977

Dopamine uptake by platelets in hepatic encephalopathy; evidence for a possible depletion of brain dopamine.

A decrease in H3-dopamine uptake was demonstrated in the blood platelets of 22 hepatic encephalopathy (HE) patients when compared to that of patients with liver cirrhosis, but without HE, and controls. There was a direct correlation between the stage of HE and the decrease in H3-dopamine uptake. As blood platelets have characteristics similar to neurons which contain amines, they have been proposed as a model for the study of amine metabolism in neurological, as well as liver diseases. A defective dopamine uptake by the HE platelets suggests that a similar biochemical derangement is, also, present in the nerve cells of the dopaminergic system. This could account for the clinical evidence of extrapiramidal dysfunction and the arousal effect of levodopa in HE. Platelets from 10 cirrhosis, but HE-free, patients had a dopamine uptake which was intermediate between the HE patients and controls. When octopamine was added at the same concentrations as in serum of HE patients, the blood platelets from five controls showed a decrease in dopamine uptake proportional to the concentration of octopamine added. Octopamine may impair dopamine uptake by platelets from HE patients.

Adult↗
PubMed1993

Cloning and characterization of the opossum kidney cell D1 dopamine receptor: expression of identical D1A and D1B dopamine receptor mRNAs in opossum kidney and brain.

Opossum kidney cells are an established epithelial cell line which is often studied as a physiological model system of renal proximal tubule function, and which has also been shown to possess dopamine receptors. To identify dopamine receptor subtypes present in renal tissue, as well as to explore the usefulness of opossum kidney cells for the study of D1 dopamine receptors and renal dopaminergic physiology, we have undertaken the cloning and characterization of the dopamine receptor expressed in this cell line. In the brains of rats and humans, two different subtypes of D1 dopamine receptors, D1A and D1B, have recently been characterized. The OK cell D1 receptor message is 4500 bp long and exhibits extensive homology with the rat and human D1A subtypes of dopamine receptors. Pharmacological experiments were performed on COS-7 cell membranes transiently transfected with this cDNA. Binding properties were compared with those reported for OK cell membranes, and comparison experiments were performed in parallel with the human D1A expressed transiently in the same system. Molecular techniques including Northern blotting, in situ hybridization, and RNase protection analysis were used to study the expression pattern of the OK cell D1 receptor message. Expression of both D1A and D1B subtypes was detected in both the opossum brain and the opossum kidney, however, the OK cell line expresses exclusively the D1A receptor subtype.

Amino Acid Sequence↗
PubMed1995

Changes in dopamine uptake and developmental effects of dopamine receptor inactivation in the sea urchin.

[3H]-dopamine ([3H]-DA) uptake was measured in the presence or absence of the catecholamine uptake inhibitor nomifensine in both unfertilized and fertilized eggs. Specific [3H]-DA uptake depended on time and [3H]-DA concentration; it was high in unfertilized eggs, declined 20-30 min after fertilization, and rose again during cleavage. Irreversible inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) resulted in a complete loss of sensitivity of egg adenylate cyclase to dopamine stimulation. In fertilized eggs treated with EEDQ for 1 hr, restoration of adenylate cyclase activity sensitive to dopamine stimulation could be observed 4 hr after the end of treatment, thus suggesting the appearance of new dopamine receptors in cleaving eggs. Short-term EEDQ treatment on unfertilized eggs, although not impairing fertilization, resulted in cleavage inhibition; the same treatment carried out soon after fertilization, on the other hand, elicited no effect on development. On the contrary, in embryos subjected to continuous treatment with EEDQ, development was impaired independent of the stage at which the treatment was started.

Adenylyl Cyclases↗
PubMed2003

Dopamine displaces [3H]domperidone from high-affinity sites of the dopamine D2 receptor, but not [3H]raclopride or [3H]spiperone in isotonic medium: Implications for human positron emission tomography.

Because the high-affinity state of the dopamine D2 receptor, D2High, is the functional state of the receptor, has a role in demarcating typical from atypical antipsychotics, and is markedly elevated in amphetamine-sensitized rats, it is important to have a method for the convenient detection of this state by a ligand. The present data show that, in contrast to [(3)H]spiperone or [(3)H]raclopride, [(3)H]domperidone labels D2High sites in the presence of isotonic NaCl in either striatum or cloned D2Long receptors, yielding a dopamine dissociation constant (1.75 nM) in agreement with that found with [(3)H]dopamine. Increased labeling of D2High sites occurred with [(3)H]domperidone after severe disruption of the cells, suggesting that [(3)H]domperidone has better access to the D2 receptor from the cytoplasmic aspect of the cell membrane. The density of the [(3)H]domperidone-labeled D2 receptors was the same as that of the [(3)H]raclopride-labeled D2 receptors, but twice the density of [(3)H]spiperone sites for human cloned D2Long receptors, compatible with the monomer-dimer concept of the D2 receptor. [(3)H]domperidone readily labels the D2High sites in postmortem human brain homogenates. Although [(3)H]spiperone or [(3)H]raclopride can occupy D2High sites, the inability of 1-10 nM dopamine to displace these ligands under isotonic conditions suggests that these ligands may not be suitable for monitoring the physiological high-affinity state of the dopamine D2 receptor by means of [(11)C]methylspiperone or [(11)C]raclopride in humans.

Animals↗
PubMed1994

Differential effects of dopamine D2 and D3 receptor antagonists in regard to dopamine release, in vivo receptor displacement and behaviour.

To establish possible functional differences between the dopamine D2 and D3 receptor we investigated the relation between the ability, for a set of nine mixed dopamine D2 and D3 receptor antagonists, to displace N, N-dipropyl-2-amino-5,6-dihydroxy tetralin (DP-5,6-ADTN) from striatal binding sites and the subsequent behavioural consequences in vivo. Dopamine D2 receptor preferring antagonists are powerful displacers of DP-5,6-ADTN from the striatum. Maximal displacement is followed by strong hypomotility. Displacement of the agonist by the D3 preferring antagonist U99194A is only partial and results in synergistic increases in locomotor activity. Superimposing haloperidol upon GBR12909 leads to a synergistic increase in striatal dialysate dopamine concentrations. This effect is absent when combining GBR12909 with the putative D3 antagonist U99194A. These data give support for the hypothesis that the dopamine D3 receptor is functionally relevant at the postsynaptic level. Here, in contrast to the D2 receptor, it is proposed to exert an inhibitory influence on psychomotor functions.

Animals↗
PubMed2004

Dopamine and glutamate dysfunctions in schizophrenia: role of the dopamine D3 receptor.

Symptoms of schizophrenia are improved by dopamine antagonists and exacerbated by dopamine-releasing agents, suggesting hyperactivity of dopamine. However, chronic blockade of glutamate neurotransmission by antagonists at the N-methyl-D-aspartate (NMDA) receptor subtype produces a pathophysiological state resembling schizophrenia. A link between cortical glutamate/NMDA deficiency and subcortical dopamine hyperactivity, particularly in the mesolimbic pathway, has been hypothesized in schizophrenia. Here we show that hyperactivity produced by NMDA receptor blockade is dependent upon stimulation of the dopamine D3 receptor subtype. Since D3 receptor antagonists and antipsychotics produced very similar effects, our results add to the growing evidence suggesting that D3 receptor blockade might produce antipsychotic effects.

Brain Chemistry↗
PubMed1998

Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat.

This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D2 mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D1 mRNA in any of the regions examined. Measurement of D2-like binding by receptor autoradiography, using the ligand [3H]YM-09151-2, revealed that both fluoxetine and desipramine increased D2-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D2-like binding in the nucleus accumbens but decreased binding in the striatum. In micro-dialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of post-synaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).

Animals↗
PubMed2005

[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine--an in vivo imaging study with a dedicated small animal SPECT.

PURPOSE: This study assessed [123I]iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. METHODS: Subsequent to baseline quantifications of D2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D2 receptors and dopamine transporters, respectively. RESULTS: Striatal baseline equilibrium ratios (V3'') of [123I]iodobenzamide binding were 1.42+/-0.31 (mean+/-SD). After pre-treatment with haloperidol and methylphenidate, V3'' values decreased to 0.54+/-0.46 (p<0.0001) and 0.98+/-0.48 (p=0.009), respectively. CONCLUSION: The decrease in [123I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [123I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [123I]iodobenzamide binding to D2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine.

Animals↗
PubMed2005

Differences in interactions with the dopamine transporter as revealed by diminishment of Na(+) gradient and membrane potential: dopamine versus other substrates.

In heterologous cells expressing the dopamine transporter (DAT), simultaneous elevation of intracellular Na(+) and depolarization of the membrane with gramicidin reduced the potency of various DAT substrates, including dopamine, d-amphetamine, beta-phenethylamine, p-tyramine, and MPP(+), in inhibiting binding of the cocaine analog [(3)H]CFT, with the greatest reduction observed for d-amphetamine. In rat striatal synaptosomes, gramicidin exerted similar effects; in addition, the potency of d-amphetamine was reduced by the Na(+)-channel activator veratridine. The latter effect was counteracted by the Na(+)-channel blocker tetrodotoxin. In broken membranes, where, as the situation with gramicidin, both sides of the non-polarized membrane were exposed to 130 mM Na(+), gramicidin was ineffective. Dopamine had a potency for membrane preparations that was not significantly different from that for control cells or synaptosomes, while other substrates had potencies for membrane preparations that were reduced to a level similar to those observed in gramicidin-treated cells or synaptosomes. These results suggest that diminishing Na(+) gradient and membrane potential may convert DAT to a conformational state that dopamine could easily bind to when gaining free access to its intracellular portion. In contrast, non-dopamine substrates may not be able to readily interact with this state from either side of the membrane.

Analysis of Variance↗
PubMed1999

Influence of food restriction on dopamine receptor densities, catecholamine concentrations and dopamine turnover in chicken brain.

To investigate further a putative role of dopamine in control of food restriction-induced behavioural stereotypies, chickens were fed during rearing on either a daily restricted ration recommended by a breeding company, twice the recommended restricted ration, or ad libitum food. They were killed at 60 days of age and their excised brains were dissected into six regions and homogenized. Densities of dopamine D1 and D2 receptors were assessed, after first estimating binding parameters for [3H]SCH 23390 (D1) and [3H]spiperone (D2) in chicken brain homogenates. Specific binding of both ligands was highest in basal telencephalon. Concentrations of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were also highest in basal telencephalon, whereas noradrenaline and adrenaline levels were highest in diencephalon. Dopamine concentration in basal telencephalon and noradrenaline concentration in diencephalon were increased significantly in response to food restriction, but no effect of feeding treatment was found in dopamine turnover, adrenaline levels, or D1 and D2 receptor densities in any brain region studied. The observed changes in brain catecholamine levels are consistent with roles for dopaminergic and adrenergic mechanisms in the control of food restriction-induced behavioural stereotypies in chickens.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Dopamine depletion with 6-OHDA enhances dopamine D1-receptor modulation of potassium currents in retinal bipolar cells.

Ascorbate modulates IK(V) of ON-type mixed rod/cone bipolar cells (Mb) in the goldfish retinal slice through a dopamine D1/G-protein/PKA-coupled mechanism. We investigated the effects of dopamine depletion with intraocular injections of 6-OHDA on IK(V) and its modulation by ascorbate over 1-7 weeks following 6-OHDA treatment. Dopamine depletion was verified by tyrosine hydroxylase immunocytochemistry. Slices were perfused in a saline containing 200 microM sodium ascorbate. One-second puffs of ascorbate-free saline (zero [AA]o), delivered through a 2-3 microm diameter pipette, were directed at the bipolar cells. IK(V) was recorded by conventional whole-cell patch-clamp methods. In normal retinas, puffs of zero [AA]o caused a rapid (<100 ms) suppression of IK(V) of about 50% that lasted for several minutes. This effect was blocked by 1 microM SCH23390 and was unaffected by 2 mM Co2+ or 5 microM spiperone. 6-OHDA treatment resulted in major effects. First, IK(V) was reduced by approximately 50% for weeks 1-6, recovering to a 20% reduction by week 7. Second, puffs of zero [AA]o enhanced IK(V) rather than suppressed it. The enhancement was blocked by SCH23390 and the PKA inhibitor, Wiptide, but was insensitive to spiperone. Third, all parts of the Mb bipolar cell (except for the axon) were sensitive to puffs of zero [AA]o in both normal and 6-OHDA-treated retinas. Fourth, bath application of 20 microM dopamine restored the amplitude of IK(V) but did not reverse the effects of puffed zero [AA]o. IK(V) was fit by two exponentials; all of the effects on IK(V) were on the amplitude of the components and not on the time constants. Chronic dopamine depletion caused reversible changes in the properties of K+ channels underlying IK(V), as well as a long-term change in the intracellular coupling mechanisms between D1-receptor activation and the modulation of IK(V).

Adrenergic Agents↗