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Biomedical subjects

N H Neff

Publications and source records attributed to N H Neff.

At least 127 records · Page 7Linked to original sources
PubMed1982

The dopamine receptor adenylate cyclase complex: evidence for post recognition site involvement for the development of supersensitivity.

The dopamine receptor adenylate cyclase complex of a rat striatal membrane preparation became more responsive to dopamine following the injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle or following the subcutaneous implantation of morphine pellets. Moreover, the membrane cyclase system was more responsive to activation by GTP, guanyl-5'-yl-imidodiphosphate and Mn-ATP. These observations suggest that both 6-OHDA and morphine induce similar biochemical changes in striatum and that the increased responsiveness arises, in part, from modification of the nucleotide regulatory and/or catalytic components of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1982

Retinal amacrine cell system tyrosine hydroxylase: the development of responsiveness to light and neuroleptic drugs.

Tyrosine hydroxylase (TH) of rat retina exists in 2 states: an activated state in the light and a basal state in the dark. In the activated state the affinity of the enzyme for the pteridine cofactor is increased. Under usual laboratory lighting conditions (12 h light--dark cycle) retinal enzyme activity of the neonate begins to appear at about 11 days of age. Enzyme activity increases in response to light at about 20 days and is fully responsive to light at 25 days. If the rats are kept in total darkness instead of normal lighting the full response of the amacrine cell system to light is delayed until about 40 days of age. The administration of neuroleptic drugs results in the activation of TH in the dark. We found that the amacrine cell system responds to neuroleptic drugs before it responds to light in animals maintained in the dark from birth.

Animals↗
PubMed1982

Adenosine measurement by a rapid HPLC-fluorometric method: induced changes of adenosine content in regions of rat brain.

We describe a rapid, sensitive method to determine brain adenosine content by HPLC. Adenosine is first reacted with chloroacetaldehyde to form fluorescent 1,N6-ethenoadenosine. The derivative is then separated from interfering compounds by HPLC on a C18 reverse-phase column and quantitated by fluorometry. We found that adenosine was rather uniformly distributed in nine brain regions of animals killed by microwave radiation. In contrast, there was an increase of adenosine in hippocampus, frontal cortex, and especially striatum of animals killed by decapitation. Moreover, adenosine content increased approximately 10-fold in the thalamus, mesencephalon, and ponsmedulla if the animals were exposed to CO2 for 1 min before they were killed by microwave radiation. Our method should be a useful aid for providing new information about the metabolic and proposed transmitter roles of brain adenosine.

Acetaldehyde↗
PubMed1982

Catabolism of endogenous dopamine in peripheral tissues: is there an independent role for dopamine in peripheral neurotransmission?

Dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), have been measured in peripheral tissues of the rat and human by gas chromatography-mass spectrometry. The content of HVA and DOPAC in peripheral tissue is higher than in blood and is usually higher than the content of DA. In the rat, chemical denervation with 6-hydroxydopamine decreased the tissue content of DOPAC. Inhibition of monoamine oxidase increased tissue DA. Apparently, in vivo, a large quantity of peripheral DA is catabolized rather than converted to norepinephrine (NE). These observations suggest that either NE synthesis is inefficient, with a large quantity of DA wasted and not converted to NE, or that DA is physiologically utilized as a neurotransmitter and/or cotransmitter in many peripheral nerves. A survey of the reported actions of DA on peripheral tissues suggests that the latter proposal is more likely.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Activation of retinal tyrosine hydroxylase: tolerance induced by chronic treatment with haloperidol does not modify response to light.

A single dose of haloperidol administered to rats in the dark increases the activity of retinal tyrosine hydroxylase. The ability of haloperidol to activate the enzyme is diminished 24 hr after terminating 22 to 30 days of treatment with haloperidol. The retinal enzyme is also tolerant to activation by treatment with chlorpromazine. In contrast, exposure of the animals to light activates the enzyme to the same extent in chronic haloperidol-treated and control animals. Thus, chronic haloperidol treatment does not modify the ability of the retinal enzyme system to respond to the physiological stimulus, light. Apparently, activation of retinol tyrosine hydroxylase by haloperidol and light occurs by independent mechanisms.

Animals↗
PubMed1982

Trans-synaptic modulation via muscarinic receptors of serotonin-containing small intensely fluorescent cells of superior cervical ganglion.

Verhofstad et al. (Verhofstad, A. A. J., H. W. M. Steinbusch, B. Penke J. Varga, and H. W. J. Joosten (1981) Brain Res. 212: 39-49) have reported that serotonin of the rat superior cervical ganglion is contained in a distinct and separate population of small intensely fluorescent (SIF) cells. We provide evidence that the serotonin-containing SIF cells are modulated, in part, by preganglionic cholinergic neurons. For example, administration of the muscarinic agonists carbachol or oxotremorine increases the content of serotonin, and the increase induced by oxotremorine is blocked by atropine. Treatment with atropine alone or decentralization of the ganglion lowers the content of serotonin. From the rate of accumulation of serotonin in the ganglion after the administration of the monoamine oxidase inhibitor pargyline, it appears that the rate of formation of serotonin is increased after oxotremorine treatment. Reserpine, p-chlorophenylalanine, or fluoxetine treatment reduces the content of serotonin in the ganglion, suggesting that the SIF cell system has properties similar to those of serotonergic neurons of the brain. We postulate that the serotonin-containing SIF cells of the rat superior cervical ganglion participate in local circuit modulation of ganglionic transmission by receiving preganglionic information via muscarinic receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Regional differences in catecholamine formation and metabolism in the rat spinal cord.

Catecholamine metabolism was assessed from the content of norepinephrine (NE), dopamine (DA) and their metabolites in various regions of the rat spinal cord during steady-state conditions and following treatment with alpha-methyl-p-tyrosine. The content of NE was rather uniform along the cord while DA was higher in the rostral portion of the cord than in the caudal portion. For both NE and DA there was a rostrocaudal decrease of their turnover rates along the cord. In the cervical cord, DA was formed at a faster rate than NE. There was no correlation between the content of catecholamine metabolites and amine turnover rates. The non-uniformity of catecholamine turnover in the cord probably arises from the fact that different regions of brain project to different regions of cord, each having a specific physiological function. Furthermore, our study provides added support for the presence of an independent DA-containing neuronal system in the spinal cord.

Animals↗
PubMed1981

Dopamine-activated adenylate cyclase of spinal cord: supersensitivity following transection of the cord.

A dopamine-activated adenylate cyclase has been identified in a membrane fraction of rat spinal cord. The concentration of dopamine producing half-maximal activation is about 5 microM and the activation is blocked by haloperidol. Apomorphine also activates the cyclase. Following transection of the cord, adenylate cyclase becomes about 5-10 times more sensitive to dopamine below the transection. The presence of dopamine-activated adenylate cyclase in the cord is consistent with reports of dopamine-containing tracts in spinal cord. This neuronal system may play an essential role in normal spinal mechanisms, in disease associated with dopaminergic neurons, as well as in the side-effects of neuroleptic drugs.

Adenylyl Cyclases↗
PubMed1981

Simultaneous determination of femtomole quantities of 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in brain using HPLC with electrochemical detection.

A simple rapid method for the determination of 5-hydroxytryptophan, serotonin (5-hydroxytryptamine), and 5-hydroxyindoleacetic acid in brain is presented. Brain proteins are precipitated with Zn(OH)2. The indoles in the supernatant are separated by HPLC in less than than 8 min on a reverse phase column and detected electrochemically. As little as 38 fmol of hydroxyindole compound can be detected and quantitated. Because the method is rapid and uncomplicated many samples can be processed in a day.

5-Hydroxytryptophan↗
PubMed1981

Polypeptide hormones and chromatin-associated proteins act as acceptors for cholera toxin-catalyzed ADP-ribosylation.

Cholera toxin catalyzed the ADP-ribosylation of the pituitary protein hormones thyrotropin (TSH), lutropin (LH), follitropin (FSH), human chorionic gonadotropin (hCG), and corticotropin (ACTH)1-24, and ADP-ribosylation of the basic proteins histone subfraction H1 and protamine. Casein and phosvitin, acidic nuclear proteins, did not act as acceptors for toxin-catalyzed ADP-ribosylation. The isolated TSH A and B subunits were tested for their ADP-ribose acceptor activity. The TSH A subunit showed fourfold greater ADP-ribose acceptor activity than the TSH B subunit. The ADP-ribose acceptor protein protamine was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis following incubation with cholera toxin under ADP-ribosylating conditions. [3H]ADP-ribose incorporated into protein from [3H]NAD migrated with the acceptor protein protamine. In the absence of added acceptor protein, the [3H]ADP-ribose incorporated into protein migrated with the A1 fragment of cholera toxin. Cholera toxin A and B subunits were isolated and tested for their ability to catalyze the transfer of ADP-ribose to protamine. The cholera toxin A subunit showed 50-fold greater ADP-ribosyltransferase activity than the B subunit. Our data indicate that a variety of adenohypophyseal hormones and regulatory proteins act as acceptors for toxin-catalyzed ADP-ribosylation. These studies may help in understanding the role of endogenous ADP-ribosyltransferases and the physiological effects of this modification of protein.

Adenosine Diphosphate Ribose↗
PubMed1981

Cyclobenzaprine: a possible mechanism of action for its muscle relaxant effect.

Intravenously administered cyclobenzaprine (CBZ) (Flexeril), a clinically used, centrally acting muscle relaxant, abolished muscle rigidity in the intercollicular decerebrate rat. In animals in which the locus coeruleus was lesioned bilaterally previously, CBZ failed to attenuate the electromyogram. In the ventral horn of the cord, which receives a dense noradrenergic innervation from the locus coeruleus, CBZ caused an increase in the metabolism of noradrenaline. In the zona intermedia of the thoracic cord, which is not innervated by the locus coeruleus, CBZ caused only minimal effects on noradrenaline metabolism. Cells in the locus coeruleus were activated by CBZ. The results indicate that in the intercollicular decerebrate rat, an intact, coerulospinal, noradrenergic projection is essential for the muscle relaxant effect of CBZ. Muscle relaxation apparently results from an activation of locus coeruleus neurones, leading to an increased release of noradrenaline in the ventral horn of the cord and the subsequent inhibitory action of noradrenaline on alpha motoneurones.

Amitriptyline↗
PubMed1981

Neuroleptic drugs activate tyrosine hydroxylase of retinal amacrine cells.

Tyrosine hydroxylase of retinal dopamine-containing amacrine cells exists in two states, a basal state in the dark and an activated state in the light. Treatment with haloperidol, chlorpromazine, clozapine or domperidone results in activation of tyrosine hydroxylase in the dark. With haloperidol, the magnitude of the activation was dose-related. After a single dose of haloperidol (3 mg/kg i.p.) enzyme activation persisted for at least 3 hr. By kinetic analysis, activation was characterized as a decrease in the Km for the pteridine cofactor. Activation by light induces similar kinetic changes. Apparently, the dopaminergic system of retina responds to neuroleptic drug treatment similar to that nigrostriatal dopaminergic system.

Adaptation, Physiological↗
PubMed1981

A simple fluorometric method for cAMP: application to studies of brain adenylate cyclase activity.

A simple fluorometric method for the determination of cAMP is presented. The fluorescent derivative is 1,N6-etheno cyclic 3,5-monophosphate (etheno-cAMP). Maximal formation of this derivative occurs after reacting cAMP with chloroacetaldehyde for 15 minutes at 100 degrees C. Fluorescent derivatives are also produced from compounds which contain a 6-amino purine. The specificity of the method resides in the use of a reverse phase/HPLC system. The derivatization as well as the fluorescent response of etheno-cAMP is linear between 2.5 and 700 picomoles of cAMP. Studies of brain adenylate cyclase by the fluorometric/HPLC method indicated that this method is comparable to the established radioenzymatic method. Thus, the present method provides a simple rapid nonradioactive means for the determination of adenylate cyclase activity.

Acetaldehyde↗
PubMed1981

Dopamine neurons of the retina: a simple method system for studying synaptic regulatory mechanisms.

In the essay we have described what we consider to be criteria for the selection of a simple mammalian model system for studying synaptic mechanisms and have shown how the dopamine-containing amacrine neuronal system of the rat retina fit these criteria. Thus, the retina contains a defined population of neurons which secrete dopamine. The neuronal activity of the dopamine-containing cells can be reproducibly controlled by the experimenter using a physiological stimulus, light. The neurons are activated by exposure to light and are relatively quiescient in the dark. We have described how this model system has been employed to study the regulation of dopamine synthesis in response to both short term and long term changes in neuronal activity. Short term exposure to light increases dopamine turnover and activates tyrosine hydroxylase, which is characterized by a decrease in the Km of the enzyme for the pteridine cofactor. After long term exposure to light the Km for the cofactor returns to the value found for animals in the dark, while the Vmax of the enzyme increases. The change of Vmax is the consequence of an increase in the specific activity of the enzyme. Evidence has also been presented illustrating the usefulness of the dopamine neuronal system of retina for studying postsynaptic mechanisms. Retina appears to contain only D-1 receptors, which are linked to adenylate cyclase. Since dopamine release in the retina can be experimentally manipulated by light, it may be possible to study the consequence of prolonged activation of receptors by dopamine on postsynaptic biochemistry.

Animals↗