Search PubMed⌕ Search

Biomedical subjects

M Hadjiconstantinou

Publications and source records attributed to M Hadjiconstantinou.

At least 91 records · Page 5Linked to original sources
PubMed1988

MPP+ depletes retinal dopamine and induces D-1 receptor supersensitivity.

Intraocular administration of 1-methyl-4-phenylpyridinium ion (MPP+) to mice resulted in a dose-dependent depletion of retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid. Pretreatment with benztropine partially prevented the MPP+-induced depletion. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was less active than MPP+ for depleting DA when administered by the same route and pretreatment with deprenyl partially prevented the depletion. Supersensitivity of retinal D-1 receptors resulted following MPP+-induced DA depletion.

1-Methyl-4-phenylpyridinium↗
PubMed1988

Acute stress or neuroleptics elicit sensorimotor deficits in MPTP-treated mice.

The present study evaluates the effects of MPTP-induced striatal DA depletions on sensorimotor behavior in mice. While MPTP produces no obvious behavioral deficits under normal conditions, acute stress (cold swim) or injection of low doses of haloperidol results in marked akinesia, catalepsy, and sensory neglect. Thus, significant behavioral impairments do accompany the neurotoxicity observed after MPTP administration in mice and render this a valuable animal model for studying mechanisms underlying Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Aromatic L-amino acid decarboxylase activity of the rat retina is modulated in vivo by environmental light.

Aromatic L-amino acid decarboxylase (AAAD) activity of rat retina is low in animals placed in the dark. When the room lights are turned on, activity rises for almost 3 h and reaches values that are about twice the values found in the dark. A study of the kinetics of the enzyme revealed that the apparent Km values for L-3,4-dihydroxyphenylalanine and pyridoxal-5'-phosphate were unchanged in light- and dark-exposed animals, whereas the Vmax increased in the light. Treating the animals with cycloheximide before exposure to light prevented the increase of enzyme activity. Immunotitration with antibodies to AAAD suggested that more enzyme molecules are present in the light than in the dark. When the room lights are turned off AAAD activity drops rapidly at first and then more slowly, suggesting that at least two processes are responsible for the fall of enzyme activity. Exposure to short periods of dark followed by light results in a rapid increase of AAAD activity. Mixing homogenates from light- and dark-exposed rats results in activity values that are less than expected, suggesting the presence of an endogenous inhibitor(s). These studies demonstrate that AAAD activity is modulated in vivo.

Animals↗
PubMed1988

Treatment with GM1 ganglioside restores striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 30 mg/kg i.p. daily for 7 days, was administered to mice. This dosage regimen resulted in an approximately 50% reduction of striatal dopamine (DA) level. Chronic administration of GM1 ganglioside (II3NeuAc-GgOse Cer), beginning between 1 to 4 days after terminating MPTP dosing, resulted in partial restoration of the striatal DA level. From dose- and time-response studies, it appeared that 30 mg/kg i.p. of GM1 administered daily for approximately 23 days resulted in an approximately 80% restoration of the DA level and complete restoration of the 3,4-dihydroxyphenylacetic acid (DOPAC) content. This dosage of GM1 also restored the turnover rate of DA in the striatum to near normal. Discontinuing GM1 treatment resulted in a fall of DA and DOPAC levels to values found in mice treated with MPTP alone. There was no evidence for regeneration of nerve terminal amine reuptake in the GM1-treated mice as evaluated by DA uptake into synaptosomes. Our biochemical findings in animals suggest that early GM1 ganglioside treatment of individuals with degenerative diseases of dopaminergic nigrostriatal neurons might be fruitful.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Pharmacological characterization of muscarinic receptors mediating inhibition of adenylate cyclase activity in the rat retina.

Incubation of the rat retina with acetylcholine resulted in about a 20 to 30% decrease of basal cyclic AMP accumulation. Oxotremorine, arecoline, [4-hydroxy-2-butynyl]trimethylammonium chloride, m-chlorocarbanilate and carbachol also inhibited cyclic AMP accumulation. Nicotine had no effect. The response was blocked by atropine and pirenzepine but not gallamine. Intraocular injection of pertussis toxin 72 hr before testing also blocked the response to acetylcholine. The presence of forskolin exaggerated the response to acetylcholine. Intraocular injection of the cholinotoxin AF64A resulted in apparent supersensitivity of the response to acetylcholine. Our results suggest that rat retina contains muscarinic M1 receptors that are coupled negatively to adenylate cyclase.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1988

Muscarinic receptor-mediated phosphoinositide hydrolysis in the rat retina.

In this report, muscarinic receptor-mediated phosphoinositide (PI) hydrolysis is characterized pharmacologically in the rat retina. In the presence of eserine, acetylcholine (ACh) elicited a concentration-dependent increase in inositol monophosphate with a calculated EC50 of about 2.8 microM. Maximum increase was achieved with about 100 microM ACh. Cholinergic receptor agonists stimulated phospholipase C-mediated hydrolysis of PI with the following rank order of potency: ACh = oxotremorine greater than McN-A-343 greater than bethanechol greater than arecoline = carbachol greater than muscarine. Oxotremorine analogs stimulated PI hydrolysis with the following rank order of potency: ACh = oxotremorine = oxotremorine-2 greater than oxotremorine-M = oxotremorine-4. Carbachol-mediated Pl hydrolysis was blocked by atropine and by the putatively selective muscarinic type 1 (M1) receptor antagonist, pirenzepine, with apparent Ki values of 0.1 and 1.0 nM, respectively. In contrast, the selective muscarinic type 2 (M2) antagonists, gallamine and AF-DX 116, failed to inhibit the action of carbachol. These findings demonstrate that stimulation of muscarinic receptors in the rat retina leads to PI hydrolysis and that these receptors appear to be M1 cholinergic receptors.

Adenylyl Cyclases↗
PubMed1987

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) accelerates the accumulation of lipofuscin in mouse adrenal gland.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes degeneration of nigrostriatal dopaminergic neurons. Recently, we reported that it also destroys dopaminergic neurons in retina and it induces the accumulation of lipofuscin. We now present morphologic and biochemical evidence that MPTP causes the accumulation of lipofuscin in the adrenal cortex. We speculate, that generation of free radicals during the transformation of MPTP to metabolites might be responsible for lipofuscin formation. MPTP-induced accumulation of lipofuscin may be a useful model for studying the biochemistry of the aging process.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Is dopamine a transmitter in the periphery?

There is now substantial experimental evidence supporting the hypothesis that a dopaminergic neuronal system is present in peripheral tissues. This evidence includes identified and characterized dopaminergic receptors, the presence of relatively large concentrations of dopamine and DOPAC in some neurons and organ systems, and the differential loss of norepinephrine or dopamine following treatment with catecholaminergic neurotoxins. There are still many studies that remain to be completed, however, existing evidence is consistent with a peripheral dopaminergic neuronal system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment decreases dopamine and increases lipofuscin in mouse retina.

The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a relatively selective neurotoxin that destroys dopamine (DA)-containing nigrostriatal neurons. We have now studied the effects of MPTP on retinal dopaminergic neurons. Acute treatment resulted in the accumulation of DA when evaluated by direct chemical analysis or histofluorescence. Chronic treatment resulted in a decrease of DA, an apparent loss of fluorescent cells, and a striking increase of lipofuscin in the retina. Thus, MPTP may be a useful drug for studying the dopaminergic neuronal system of retina and the possible link between neurons and the accumulation of lipofuscin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat.

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.

Acetylcholine↗
PubMed1986

Epinephrine synthesis in the PC12 pheochromocytoma cell line.

PC12 is a rat pheochromocytoma cell line which has been increasingly used as a model system for both neural differentiation and chromaffin cell function. PC12 cells have been reported to synthesize dopamine and norepinephrine, but not epinephrine. We have found that PC12 cells do synthesize small amounts of epinephrine and that dexamethasone increases both epinephrine content as well as phenylethanolamine-N-methyltransferase (PNMT) activity. These results suggest that the PC12 cell line may be useful in the investigation of the regulation of PNMT.

Adrenal Gland Neoplasms↗
PubMed1986

Treatment with GM1 ganglioside increases rat spinal cord indole content.

Chronic treatment with GM1 ganglioside apparently increases serotonin metabolism in the spinal cord of control and hemitransected rats. Dopamine metabolism is stimulated below a hemitransection with GM1 treatment. These observations are consistent with reports that GM1 promotes regrowth of neurons after experimental lesions of brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Intracerebroventricular administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium ion (MPP+) decrease dopamine and increase acetylcholine in the mouse neostriatum.

We found that both MPTP and its metabolite MPP+ decrease dopamine and increase acetylcholine content of mouse neostriatum when administered intracerebroventricularly (ICV). These observations support the notion that MPP+ may be the active neurotoxin formed in brain after MPTP administration. They also suggest that cholinergic mechanisms may be a target of the neurotoxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Exposure to light accelerates the formation of dopamine from exogenous L-dopa in the rat retina.

Dopaminergic neurons of retina are activated when rats are placed in a lighted environment. L-DOPA, the precursor of dopamine, was administered to rats that were housed either in the light or the dark. In the light more dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were formed from L-DOPA when compared with animals given the same dose of L-DOPA, but kept in the dark. Our results suggest that the in vivo decarboxylation of DOPA may be modulated by neuronal activity in the rat retina.

Animals↗
PubMed1985

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine increases acetylcholine and decreases dopamine in mouse striatum: both responses are blocked by anticholinergic drugs.

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathology and clinical symptoms that resemble Parkinsonism in primates and humans. In mice it induces a long-lasting depletion of neostriatal 3,4-dihydroxyphenylethylamine (dopamine) content. Using the mouse, we found that MPTP induces a fall of dopamine and a rise of acetylcholine in the neostriatum. Both responses to MPTP can be blocked by prior treatment with atropine or trihexyphenidyl.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Aging and diurnal rhythms of pineal serotonin, 5-hydroxyindoleacetic acid, norepinephrine, dopamine and serum melatonin in the male rat.

Pineal serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography with electrochemical detection and serum melatonin was measured by radioimmunoassay in rats aged 3 weeks, 8 weeks and 18 months. They were killed either at mid-light or mid-dark of a 12 h light:12 h dark cycle. Diurnal rhythms were observed for 5-HT and 5-HIAA in all ages studied while those for NE and DA were not observed in the 18-month-old animals. Pineal 5-HT and 5-HIAA were higher in 3-week-old rats at mid-dark, and lower at mid-light than in older animals. The pineal content of NE was lower in the 3-week-old rats at mid-dark and mid-light compared with that in the 8-week-old while the DA content was lower at mid-dark. In addition, pineal 5-HT, 5-HIAA, NE and DA were lower in the 18-month-old than in the 8-week-old animals at mid-dark. At mid-dark serum melatonin levels showed an age-related decrease. This study shows that an age-related decrease of pineal 5-HT, 5-HIAA, NE and DA can only be demonstrated at mid-dark and that the age-related decrease of melatonin may not be due to a decrease in sympathetic activity.

Aging↗
PubMed1984

Chronic treatment with diisopropylfluorophosphate increases dopamine turnover in the striatum of the rat.

Following the administration of a single dose of diisopropylfluorophosphate (DFP) there is a rise of acetylcholine (ACh) in the rat striatum and frontal cortex. With chronic treatment, striatal ACh content returns to normal, but frontal cortex ACh remains elevated. In striatum but not frontal cortex, there is a rise of dopamine (DA) content and turnover after chronic DFP treatment. We speculate that DA content and turnover are increased after chronic DFP because the nigrostriatal neuronal feedback loop and local feedback loops are activated to compensate for increased cholinergic tone.

3,4-Dihydroxyphenylacetic Acid↗