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Biomedical subjects

W Lovenberg

Publications and source records attributed to W Lovenberg.

At least 163 records · Page 9Linked to original sources

Effect of antihypertensive therapy on lysine incorporation into vascular protein of the spontaneously hypertensive rat.

Young spontaneously hypertensive rats (SHR) were either treated with hydralazine or hexamethonium or splanchnicotomized, so that the development of hypertension was effectively arrested for two weeks. The rate of incorporation of 3H-lysine into non-collagenous proteins in vivo of the heart, aorta and mesenteric arteries was determined in the treated SHR, as well as control SHR and normal Wistar/Kyoto (WK) rats. The lysine incorporation into the non-collagenous protein of mesenteric arteries was increased in 8-week-old SHR as compared with WK rats. Teh elevated lysine incorporation in the SHR was abolished by treatment with hexamethonium or by splanchnicotomy, but was not affected by treatment with hydralazine. It is suggested that sympathetic innervation is important fot the increased synthesis of vascular non-collagenous protein during the early hypertensive phase in the SHR.

Animals↗

NIH conference. Dopamine- -hydroxylase. Basic and clinical studies.

Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzyme's action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.

Adolescent↗

ATP, cyclic AMP, and magnesium increase the affinity of rat striatal tyrosine hydroxylase for its cofactor.

Treatment of rat striatal tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] with conditions optimal for protein phosphorylation results in the reduction of the tyrosine hydroxylase Km for the cofactor 6-methyltetrahydropterin from 0.50 mM to 0.16 mM. This reaction is dependent upon ATP, 3':5'-cAMP, and Mg++ and causes a marked decrease in the sensitivity to end-product inhibition. Other brain regions and the adrenal gland show a similar response.

Adenosine Triphosphate↗

A developmental study of the effects of 5,7-dihydroxytryptamine on regional tryptophan hydroxylase in rat brain.

Tryptophan hydroxylase activity rises rapidly after birth in 5 distinct regions of the rat CNS. Near-adult levels of activity are recorded by 22 days of age in the cell-body rich regions of the brainstem and by 42 days in the terminal-rich areas, hypothalamus and remaining forebrain. The intracisternal injection of 40 mug 5,7-dihydroxytryptamine on day 2 after birth results in a near-total depletion of tryptophan hydroxylase in all CNS regions analyzed 6 or 12 days after drug administration. Enzyme activity recovers (to 11-24% of age matched controls) between day 12 and 20 after 5,7-dihydroxytryptamine in hypothalamus, midbrain and pons medulla oblongata. The growth of 5,7-DHT-treated animals is retarded between 3 and 40 days after drug administration.

Age Factors↗

Electron transport to clostridial rubredoxin: kinetics of the reduction by hexaammineruthenium(II), vanadous and chromous ions.

The rate constants (25 degrees , M(-1) sec(-1)), activation enthalpies (kcal/mol), and activation entropies (e.u.) for the second-order reduction of oxidized clostridial rubredoxin by Ru(NH(3))(6) (2+), V(H(2)O)(6) (2+), and Cr(H(2)O)(6) (2+) at I = 0.10 have been determined or estimated to be 9.5 x 10(4), approximately 1.4, approximately -31 (pH 6.3-7.0); 1.6 x 10(4), 0.1, -40 (pH 3.5-4.5); and 1.2 x 10(3), approximately 0, approximately -44 (pH 3.5-4.0), respectively. Ionic strength dependencies for the vanadium reaction are suggestive of a direct interaction of the reductants with the Fe(SR)(4) (-1) site of oxidized rubredoxin. The results are consistent with outer-sphere mechanisms for all three reductants and an especially high inherent outer-sphere reactivity of rubredoxin. This high reactivity level is attributed to the low activation enthalpy demands of the iron-sulfur site of rubredoxin. Thus, the possibility is raised that the rate of reaction of rubredoxin with its physiological counterparts may be determined largely by the activation entropy demands imposed by the physiological reactant. Evidence is presented in support of an absolute entropy decrease of about 7.5 e.u. on going from oxidized to reduced rubredoxin, which is presumably attributable to the charge increase from Fe(SR)(4) (1-) to Fe(SR)(4) (2-) at the redox site.

Chromium↗

Studies on the carbohydrate moiety of dopamine beta-hydroxylase: interaction of the enzyme with concanavalin A.

Dopamine beta-hydroxylase [EC 1.14.17.1; 3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating)], a glycoprotein, was found to interact strongly with the plant lectin, concanavalin A. This interaction did not appear to alter the catalytic properties of the enzyme and did not prevent interaction of the protein with specific antibodies. Dopamine-beta-hydroxylase is adsorbed to concanavalin A covalently bound to Sepharose and can be eluted with alpha-methylmannoside. The enzyme is catalytically active when it is immobilized on a concanavalin A-Sepharose column. Enzymic removal of four of seven mannose residues present in the monomer does not result in the loss of any catalytic activity. It is concluded that the active site is not near the point of carbohydrate attachment on the molecule and that this may be of significance in orienting the enzyme on the vesicular membrane.

Adrenal Glands↗

Effects of dietary sodium and of acute saline infusion on the interrelationship between dopamine excretion and adrenergic activity in man.

The effects of dietary sodium and of saline infusion on urinary dopamine and norepinephrine and on the relationship of these catecholamines to adrenergic activity were determined. In seven normal subjects on a 9-meq sodium intake, urinary dopamine and norepinephrine were 136+/-18 (SE) and 37.4+/-5.3 mug/day, respectively. When sodium intake was increased to 209 or 259 meq/day, urinary dopamine increased to 195+/-20 mug/day (P<0.01) whereas urinary norepinephrine decreased to 21.1+/-3.0 mug/day (P<0.01). Infusion of saline in seven subjects increased sodium excretion and urinary dopamine (from 2.18+/-0.22 to 2.79+/-0.19 mug/20 min, P<0.01), but decreased plasma dopamine-beta-hydroxylase by 33% and urinary norepinephrine insignificantly. The clearance of inulin and p-aminohippurate did not change significantly and filtration fraction was the same. The data indicate that an increase in dietary sodium or infusion of saline results in an apparent decrease in adrenergic activity and an increase in urinary dopamine. Dopamine excretion would thus appear to relate inversely to adrenergic activity and to parallel sodium excretion. These findings suggest a possible role for dopamine and norepinephrine in the regulation of renal sodium excretion.

Adult↗