Search PubMed⌕ Search

Biomedical subjects

W Lovenberg

Publications and source records attributed to W Lovenberg.

At least 91 records · Page 5Linked to original sources
PubMed1981

Specific and sensitive radioimmunoassay for 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG).

Antibodies that specifically bind the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) were produced in rabbits after injection of a derivative of MOPEG conjugated with bovine thyroglobulin. A sensitive radioimmunoassay was devised with this antiserum, in which as little as 0.5 nanogram of MOPEG can be accurately measured with a final antibody dilution of 1:180. The antibody appears to be specific for MOPEG, since tritiated MOPEG was not displaced from the antibodies by norepinephrine, epinephrine, dopamine, serotonin, or their major metabolites including MOPEG-sulfate (333 nanograms each).

Animals↗
PubMed1981

Blood pressure responses to local application of serotonergic agents in the nucleus tractus solitarii.

The effects of serotonin applied directly to the region of the medulla oblongata which contains the nucleus tractus solitarii, nucleus intercalatus, nucleus originis dorsalis vagi and the nucleus originis nervi hypoglossi were investigated in anesthetized rats. A dose dependent increase in blood pressure with variable changes in heart rate was observed after unilateral application of serotonin into the nucleus tractus solitarius. The serotonergic antagonists, 2-bromolysergic acid diethylamide (locally applied) and metergoline (systemically administered) significantly attenuated the serotonin-induced pressor response. Fluoxetine, a serotonin uptake inhibitor, significantly enhanced the magnitude of the pressor response, but did not prolong it. The present data suggest that enhancement of serotonergic activity in the region of the nucleus tractus solitarius produces a neurogenic pressor response.

Animals↗
PubMed1981

Increased number of PNMT-immunofluorescent nerve cell bodies in the medulla oblongata of stroke-prone hypertensive rats.

An antiserum to bovine adrenal PNMT was used to identify PNMT-containing nerve cell bodies in the medulla oblongata of 4-week-old normotensive Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The regional distribution of PNMT cells and the total number of PNMT cell profiles in tranverse sections of the medulla were examined in each of the two strains. While there was no significant difference in the pattern of distribution of the cells, both the number of PNMT cell profiles per section and the total number seen in all sections of the medulla were significantly higher in the hypertensive rats. The increase in counts of PNMT cell profiles in the medulla suggests that there is a genetic difference in the number of central adrenaline neurons in these hypertensive rats. This is supported by the finding of similar increases of PNMT enzyme activity in the medulla of both stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats compared with Wistar-Kyoto rats.

Animals↗
PubMed1981

Haloperidol-induced reduction of nigral substance P-like immunoreactivity: a probe for the interactions between dopamine and substance P neuronal systems.

Protracted blockade of dopamine receptors by haloperidol has been shown to cause a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect is used to study the mechanisms whereby the dopaminergic and substance P systems interact. Data presented in this paper suggest that 1) blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop, 2) destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol, 3) several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and 4) substance P striatal-nigral circuits continue to respond to dopaminergic input after kainic acid lesions in the anterior striatum, whereas properly placed mechanical striatal-nigral lesions appear to be effective in preventing this interaction. The data support a dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry and suggest that his pathway must be accounted for when studying the interactions of transmitter systems within this locomotor center.

Animals↗
PubMed1980

The hypotensive effect of centrally administered tyrosine.

Intraventricular injection of 15 microgram L-tyrosine results in a significant reduction in blood pressure in the spontaneously hypertensive rat. An increase in the turnover of norepinephrine as indexed by MOPEG-SO4 is observed concurrently. The data are consistent with the previously suggested depressor role of certain central noradrenergic neurons.

Animals↗
PubMed1980

The hypotensive action of 3-deaza-adenosine.

The effects of 3-deaza-adenosine on the cardiovascular system was investigated in normotensive (WKY) and spontaneously hypertensive rate (SHR). This compound (50 mg/kg i.p. 2X) significantly lowers blood pressure in both groups of animals, an effect which lasts for up to 2 h. The hypotensive effect is not affected by ganglion blockade, and appears to be due in part to a direct effect on blood vessels. While the response is similar to that seem with adenosine, it is more long-lasting. The results of this study suggest a potential role for this compound or analogues of its as possible antihypertensive agents.

Animals↗
PubMed1980

Tryptophan hydroxylase. The role of oxygen, iron, and sulfhydryl groups as determinants of stability and catalytic activity.

Tryptophan hydroxylase (EC 1.14.16.4) from rat mid-brain is inactivated upon exposure to oxygen. The degree of inactivation is dependent both on the temperature and partial pressure of oxygen to which the enzyme is exposed. Furthermore, molecular oxygen, and not an oxygen or hydroxyl radical, is responsible for the inactivation. Sulfhydryl compounds and reductants partially protect the hydroxylase from inactivation by oxygen. Enzyme inhibited by oxygen can be reconstituted by anaerobic incubation in the presence of dithiothreitol and Fe2+ at 25 degrees C and in some experiments the inclusion of inorganic sulfide, in addition to dithiothreitol and Fe2+, led to even greater recoveries of activity. Preincubation of tryptophan hydroxylase with various sulfhydryl reagents or disulfide compounds also produces inactivation which can be rapidly reversed by dithiothreitol. The substrate tryptophan protects the enzyme from inactivation by sulfhydryl reagents and disulfides but not from inactivation by oxygen. Finally, the enzyme was inhibited by a variety of iron chelators. These results suggest that the catalytic activity of tryptophan hydroxylase is dependent on the oxidation-reduction status of--SH groups and iron sites, which are probably located at the catalytic (substrate binding) site of the enzyme.

Animals↗
PubMed1980

Dopamine beta-hydroxylase in CSF. Relationship to personality measures.

Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was measured in the CSF of 32 subjects. Those individuals with a low level of DBH in the CSF had significantly elevated profiles on the Minnesota Multiphasic Personality Inventory, suggesting a relationship between the central noradrenergic system and some aspects of personality in man.

Adolescent↗
PubMed1980

Inhibition of dopamine-beta-hydroxylase by alternative electron donors.

The alternative electron donors ferrocyanide and hydroquinone have been shown to also act as inhibitors of dopamine-beta-hydroxylase (3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1). Hydroquine shows uncompetitive inhibition with respect to ascorbate and competitive inhibition with respect to tyramine. Ferrocyanide shows uncompetitive inhibition with respect to ascorbate and mixed type inhibition with respect to tyramine. Inhibition by ferrocyanide at concentrations at or above 2.5 . 10(-5) M was prevented by 2.5 . 10(-6) M cupric ion. These results indicate that the inhibitory action of these alternative electron donors is due to their interaction with a reduced enzyme species. The potency of inhibition of dopamine-beta-hydroxylase by both ferrocyanide and hydroquinone is dependent on the degree of protonation of a group in the enzyme having a pKa of 5.3.

Ascorbic Acid↗
PubMed1980

Calcium-regulated phosphorylation in synaptosomal cytosol: dependence on calmodulin.

Calcium stimulated the phosphorylation of several specific synaptosomal cytosolic proteins. The effects of calcium were both concentration and time dependent and were most apparent for proteins with molecular weights of 50,000, 55,000, and 60,000. Exogenous calcium (1.0-100 microM) enhanced the net incorporation of phosphate into protein by as much as 23-fold. In the absence of added calcium, the calcium chelator [ethylenebis(oxyethylenenitriolo)]tetraacetic acid did not lower the phosphorylation of any protein below control levels. The antipsychotic, fluphenazine (1.0-100 microM), caused a concentration-dependent decrease in calcium-stimulated protein phosphorylation. When the heat-stable calcium-binding protein, calmodulin, was removed from synaptosomal cytosol by affinity chromatography on fluphenazine-Sepharose, calcium-stimulated protein phosphorylation was abolished. Responsiveness to calcium could be restored by the addition of calmodulin to the phosphorylation assay. These results indicate that calcium-dependent protein kinases are of major importance in regulating the phosphorylation of specific cytosolic proteins in neuronal tissue. Furthermore, it would appear that one of the three substrates under investigation is specific to synaptosomal cytosol whereas the other two are present in both the cytosol and membrane fractions.

Animals↗
PubMed1980

Activation of brain tryptophan hydroxylase by ATP-MG2+: dependence on calmodulin.

Tryptophan hydroxylase [tryptophan 5-monooxygenase, L-tryptophan,tetrahydropterin:oxygen oxidoreductase (5-hydroxylating), EC 1.14.16.4] is activated by phosphorylating conditions (ATP-Mg2+) in a calcium-dependent, cyclic AMP-independent manner. Addition to the phosphorylation reaction of certain antipsychotic drugs that bind to calmodulin, the heat-stable calcium-binding protein, prevents the activation of tryptophan hydroxylase by ATP-Mg2+ in a concentration-dependent fashion. External addition of purified calmodulin protects the enzyme from the drug-induced effects. Calmodulin-free tryptophan hydroxylase prepared by affinity chromatography on fluphenazine-Sepharose is not activated by ATP-Mg2+ whereas addition of calmodulin to calmodulin-free enzyme restores the responsiveness of the hydroxylase to ATP-MG2+ only in the presence of Ca2+. These results indicate that the activation of tryptophan hydroxylase by phosphorylating conditions is dependent on both calcium and calmodulin.

Adenosine Triphosphate↗