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.

Administration of GM1 ganglioside eliminates neuroleptic-induced sensorimotor deficits in MPTP-treated mice.

Injection of a low dose of haloperidol, that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and sensory neglect in MPTP-treated mice. GM1 ganglioside treatment eliminates all of these behavioral impairments and also partially restores striatal dopamine content. These observations suggest that the MPTP-treated mouse may be a valuable model for studying mechanisms underlying parkinsonism and that administration of GM1 ganglioside may be an effective therapy.

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.

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.

A dominant trifluoperazine resistance gene from Saccharomyces cerevisiae has homology with F0F1 ATP synthase and confers calcium-sensitive growth.

The antipsychotic drug trifluoperazine has been long considered a calmodulin inhibitor from in vitro studies but may function in vivo as a more general inhibitor by disturbing ion fluxes and altering the membrane potential. Resistance to trifluoperazine can arise in Saccharomyces cerevisiae cells by alterations in at least three distinct genetic loci. One locus, defined by a spontaneous dominant trifluoperazine resistance mutation (TFP1-408), was isolated and sequenced.

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.

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.

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.

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.

Inhibitory Effects of a Pectin-Enriched Tomato Cell Wall Fraction on Agrobacterium tumefaciens Binding and Tumor Formation.

A pectin-enriched soluble cell wall fraction (CWF) prepared from suspension cultured tomato cells inhibits binding of Agrobacterium tumefaciens to these cells. It was hypothesized that the CWF contains the plant surface binding site for A. tumefaciens (NT Neff, AN Binns 1985 Plant Physiol 77: 35-42).

An approximation for the distribution of the scan statistic.

The scan statistic evaluates whether an apparent cluster of disease in time is due to chance. The statistic employs a 'moving window' of length w and finds the maximum number of cases revealed through the window as it scans or slides over the entire time period T. Computation of the probability of observing a certain size cluster, under the hypothesis of a uniform distribution, is infeasible when N, the total number of events, is large, and w is of moderate or small size relative to T.

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.

Administration of GM1 ganglioside restores the dopamine content in striatum after chronic treatment with MPTP.

The dopamine (DA) content of the mouse striatum thirty days after treatment with MPTP is significantly reduced. GM1 ganglioside administration during the thirty day period results in a partial restoration of the striatal DA content.

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.

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.

Differentiation of noradrenergic and dopaminergic neurons in the cardiovascular system.

Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and norepinephrine (NE) are present in the rat cardiovascular system. All of the catechols can be partially depleted by administering 6-hydroxydopamine (6-HODA). When animals are pretreated with desipramine before 6-HODA, there is a selective partial depletion of DA and DOPAC.

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.

Isolation and characterization of mutations in the beta-tubulin gene of Saccharomyces cerevisiae.

Of 173 mutants of Saccharomyces cerevisiae resistant to the antimitotic drug benomyl (BenR), six also conferred cold-sensitivity for growth and three others conferred temperature-sensitivity for growth in the absence of benomyl. All of the benR mutations tested, including the nine conditional-lethal mutations, were shown to be in the same gene. This gene, TUB2, has previously been molecularly cloned and identified as the yeast structural gene encoding beta-tubulin.

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.

Photoaffinity labeling of the GABAA receptor with [3H]muscimol.

Muscimol is one of the most potent agonist ligands at the gamma-aminobutyric acidA (GABAA) receptor. Analysis of its chemical structure showed it to be a candidate for photoaffinity labeling. In practice, UV irradiation at 254 nm both changed the UV spectrum of muscimol and induced an irreversible binding of [3H]-muscimol to rat cerebellar synaptosomal membrane.

Agrobacterium tumefaciens Interaction with Suspension-Cultured Tomato Cells.

Adherence of Agrobacterium tumefaciens to suspension-cultured tomato cells has been characterized using a quantitative binding assay. Saturable binding of radiolabeled A. tumefaciens to plant cells resulted in 100 to 300 bacteria bound per cell.

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.

Co-localized adenosine A1 and gamma-aminobutyric acid B (GABAB) receptors of cerebellum may share a common adenylate cyclase catalytic unit.

In synaptosomal membranes from rat cerebellum, additive responses to adenylate cyclase activity are observed between the beta adrenergic receptors present on the Purkinje cells and the adenosine A-1 receptors or gamma-aminobutyric acid B (GABAB) receptors, which are both associated with the granule cells. In contrast, nonadditive responses are found with the activation of the adenosine A-1 and the GABAB receptors. Because both receptors are mainly associated with the same cell type, the nonadditive response indicates an interaction between the adenosine A-1, GABAB receptors and the adenylate cyclase.