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N H Neff

Publications and source records attributed to N H Neff.

At least 91 records · Page 5Linked to original sources
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

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

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. After 10 min of irradiation, using 10 nM [3H]muscimol, the specific portion of this binding was 270 fmol/mg protein. (Nonspecific binding was defined as that arising in the presence of 1 mM GABA.) Specific binding increased asymptotically up to 100 nM [3H]muscimol. Irradiation of the membranes themselves did not significantly alter the KD or Bmax of reversible [3H]muscimol binding. However, irradiation of [3H]muscimol reduced its capacity subsequently to photolabel the membranes by 86 +/- 3%. Dose-dependent inhibition of binding was observed with muscimol, GABA, and bicuculline methiodide; with 10 nM [3H]muscimol maximum inhibition was 70% of total labeling and the order of potencies of these three compounds was characteristic of labeling to the GABAA receptor. Baclofen, l-glutamate, and diazepam exerted no effect at high concentrations. SDS-PAGE of the photolabeled membranes indicated specific incorporation of radioactivity into two molecular-weight species. One failed to enter the separating gel, implying a molecular weight greater than 250,000 daltons (250 kD). The molecular weight of the other was identified by fluorography to be about 52,000 daltons (52 kD).

Affinity Labels↗
PubMed1985

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. The present study suggests that the nonadditivity results from a limited number of adenylate cyclase catalytic units, which both receptor systems share. This conclusion was derived indirectly by showing that 1) a GABAB agonist did not affect the adenosine A-1 recognition site; 2) both receptors additively activated the high-affinity guanosine 5'-triphosphatase, which is believed to reflect the activation of the inhibitory guanine nucleotide unit; and 3) the nonadditivity was still observed after stimulation of adenylate cyclase activity with forskolin.

Adenosine↗
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↗
PubMed1984

Spinal cord serotonin: a biochemical and immunohistochemical study following transection.

The serotonin (5-HT) content of rat spinal cord was studied following complete cord transection, transverse hemisection and rhizotomy by high pressure liquid chromatography-electrochemical detection (HPLC-EC) chromatography and immunohistochemically with rabbit anti-5-HT antiserum. Spinal cord 5-HT decreased but did not disappear after complete cord transection when studied 5 or 10 days after lesioning. Indeed the indole content 5 or 10 days after section were similar. Below the transection 5-HT-like immunoreactive neuronal elements were present, appeared normal but were significantly reduced compared with control cord. Although neuronal fibers were present after transection, no immunoreactive neuronal cell bodies were observed. The neuronal elements remaining after transection were capable of synthesizing and metabolizing 5-HT as evidenced by elevated 5-HT and decreased 5-hydroxyindoleacetic acid (5-HIAA) after inhibition of monoamine oxidase. Complete cord transection resulted in a fall of 5-HT in the ventral roots suggesting that they contain efferent 5-HT elements that originate above the transection. Rhizotomy plus cord transection did not change cord indole content more than transection alone demonstrating that the indoles that remain in the cord after transection did not originate from peripheral afferent 5-HT neurons. Hemitransection resulted in partial loss of immunoreactive neuronal elements on the cut side, but 5-HT-like immunoreactive nerve fibers were observed crossing within the cord from the intact side by the spinal canal. Analysis of indole content in the hemitransected cord were consistent with crossing of 5-HT fibers within spinal segments. Our studies, taken together with reports by other laboratories, support the notion that significant 5-HT elements remain in the spinal cord after transection. These elements appear normal morphologically and biochemically.

Animals↗
PubMed1984

Catecholamine systems of retina: a model for studying synaptic mechanisms.

The retina contains three catecholamine neurotransmitters: dopamine (DA); norepinephrine (NE); and epinephrine (EPI). DA and EPI appear to be associated with separate amacrine neurons that directly participate in the visual process. NE, in contrast, appears to be associated primarily with the sympathetic nerves that innervate the blood vessels of the retina. We present a synopsis of the anatomy, physiology, biochemistry and pharmacology of these retinal neurons. We also suggest that some diseases usually associated with catecholamines of brain may have their counterpart in retina.

Adenylyl Cyclases↗
PubMed1984

Spinal cord acetylcholine content: the consequence of transection or treatment with the neurotoxin 6-aminonicotinamide.

The distribution of choline (Ch) and acetylcholine (ACh) within the rat spinal cord was found to be rather uniform with values for Ch of about 280 pmol/mg protein and for ACh of about 250 pmol/mg protein. Cord transection at the T10-11 level did not reduce ACh below the lesion but there was about a 30% decrease of ACh in the thoracic region suggesting the presence of cholinergic fibers that ascend and terminate within the cord. Treatment of rats with the neurotoxin 6-aminonicotinamide resulted in spastic hindlimb paralysis and a loss of ACh in the lumbar region of the cord.

6-Aminonicotinamide↗
PubMed1984

Acetylcholine measurement by high-performance liquid chromatography using an enzyme-loaded postcolumn reactor.

Choline oxidase and cholinesterase were found to retain their activity for 1-2 weeks at room temperature while adsorbed to a commercially available anion-exchange cartridge. These enzymes convert acetylcholine to H2O2. Acetylcholine can be measured in tissue extracts by separation at pH 7 on a polymeric reverse-phase high-performance liquid chromatography column, conversion of acetylcholine to H2O2 on a postcolumn enzyme-loaded anion-exchange cartridge, and electrochemical detection of the H2O2 formed.

Acetylcholine↗
PubMed1984

Correlation between histamine-induced neuronal excitability and activation of adenylate cyclase in the guinea pig hippocampus.

In a homogenate of guinea pig hippocampus histamine activated adenylate cyclase and in a hippocampal slice preparation it increased the firing rate of pyramidal cells in the CA3 region. Both activities were apparently mediated by H2 receptors. The concentration of histamine and of the H2 receptor agonist, impromidine, required to stimulate activity was similar in each test preparation with impromidine being about 100-fold more potent than histamine. Moreover, the H2 receptor antagonists, cimetidine and ICIA 5165, each reversed the activation by histamine of the two test preparations, with ICIA 5165 being about 100-fold more potent than cimetidine. Thus, there is a correlation between activation of cyclase and neuronal excitability induced by histamine. These observations support a large body of evidence suggesting that histamine is a neurotransmitter or modulator in the CNS.

Action Potentials↗
PubMed1984

Immunohistochemical evidence for epinephrine-containing retinal amacrine cells.

The enzyme for the synthesis of epinephrine, phenylethanolamine-N-methyltransferase, has been localized, by an indirect immunofluorescent staining method, to a subpopulation of amacrine cells in the rat retina. The immunoreactive cells are located primarily in the inner nuclear layer and send a single process to the inner plexiform layer. Most of the immunoreactivity is found in the center of the inner plexiform layer. A small percentage of immunoreactive cell bodies were found in the inner plexiform layer and occasionally cells were observed in the ganglion cell layer. These epinephrine-containing amacrine cells are morphologically distinct from the dopamine-containing amacrine cells previously described by formaldehyde fluorescence and we speculate from reports in the literature that epinephrine-containing amacrine cells may play a role in modulating the activity of dopamine-containing amacrine cells.

Animals↗