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Biomedical subjects

W Lovenberg

Publications and source records attributed to W Lovenberg.

At least 73 records · Page 4Linked to original sources
PubMed1983

Action of substance P on the working rat heart.

The effect of substance P (SP) on the cardiodynamics of the isolated working rat heart perparation was examined. The peptide over the concentration range of 10(-8) to 10(-6) M was found to have no influence on aortic pressure, cardiac output, or cardiac work. However, a 10-15% reduction in coronary flow was observed at 1 x 10(-6) M substance P. Octapeptide substance P (SP4-11) exhibited a similar vasoconstrictive action. The IC50 of SP4-11 was 2 x 10(-13) M compared to an IC50 of 3.5 x 10(-8) M for substance P. Perfusion of the heart in the presence of bacitracin (1 x 10(-4) M), a protease inhibitor, prevented the reduction in coronary flow observed in the presence of substance P. By contrast, the reduction in coronary flow produced by octapeptide substance P was not altered by the presence of bacitracin. Thus, it appears that a C-terminal fragment such as SP4-11 may be responsible for the observed decrease in coronary flow.

Animals↗
PubMed1983

Phosphorylation of brain cytosol proteins. Effects of phospholipids and calmodulin.

Calmodulin was removed from brain cytosol by DEAE-52 chromatography or by affinity chromatography employing fluphenazine-Sepharose. The substrates phosphorylated by endogenous protein kinase after chromatography differed depending on the method used, and both chromatographic methods altered the phosphorylation pattern as compared to untreated cytosol. Cytosol, chromatographed on fluphenazine-Sepharose, retained most of the characteristics of untreated cytosol. Both calmodulin and phospholipids increased the phosphorylation of specific but separate brain cytosol proteins in a Ca2+-dependent manner. The effects of phospholipids could be mimicked by the detergent, sodium dodecyl sulfate, and the hydrophobic probe, 8-anilino-1-naphthalenesulfonate. Furthermore, the calmodulin-induced increase in phosphorylation, but not that produced by phospholipids, was blocked by 8-anilino-1-naphthalenesulfonate. These results suggest that the effects of phospholipids may not be due to the presence of a specific phospholipid-sensitive protein kinase in cytosol, but rather to a general interaction of hydrophobic probes with either specific substrate proteins or with the Ca2+-calmodulin-dependent protein kinase itself.

Animals↗
PubMed1983

Determination of some molecular parameters of tyrosine hydroxylase from rat adrenal, rat striatum, and human pheochromocytoma.

The molecular parameters of tyrosine hydroxylase (EC 1.14.16.2) from rat adrenal, rat striatum, and human pheochromocytoma were determined by combined gel filtration and sucrose gradient ultracentrifugation. The enzyme from rat adrenal has a calculated molecular weight of 228,000, a Stokes radius of 60.9 A, a sedimentation coefficient of 9.10S, and a frictional ratio of 1.39. The enzyme from rat striatum has a calculated molecular weight of 210,000, a Stokes radius of 54.3 A, a sedimentation coefficient of 9.38S, and a frictional ratio of 1.28. Tyrosine hydroxylase from human pheochromocytoma tissue has a calculated molecular weight of 255,000, a Stokes radius of 68.2 A, a sedimentation coefficient of 9.08S, and a frictional ratio of 1.50. These results indicate that the tyrosine hydroxylases from central and peripheral tissue in the rat are quite similar although the human enzyme appears to be significantly larger.

Adrenal Gland Neoplasms↗
PubMed1982

Effect of unilateral carotid ligation on brainstem PNMT activity.

Phenylethanolamine N-methyltransferase (PNMT) activity in the C1 and C2 regions of the brainstem was assayed in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without unilateral carotid artery ligation. PNMT activity was significantly higher in SHR than in WKY (P less than 0.01). PNMT activity in the C1 and C2 regions on non-ligated side in both WKY and SHR was significantly elevated compared with that on the ligated side. These results indicate that the activity of PNMT in adrenergic neurons may respond to baroreflex activation and that adrenergic neurons may be involved in blood pressure regulation.

Animals↗
PubMed1982

Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum.

Incubation, for 30 min, of striatal slices with 10 microM dopamine, 10 microM apomorphine, or 10 microM SKF 38393 decreased dopamine-stimulated adenylate cyclase activity by 50-60%. This loss in dopamine-stimulated enzyme activity appears to be mediated by a persistent occupancy of recognition sites of the D-1 receptor because: (i) at 10 microM, SKF 38393, a selective D-1 receptor agonist, facilitates desensitization and Ly 141865, a selective D-2 receptor agonist, fails to elicit desensitization of dopamine-dependent adenylate cyclase; and (ii) preincubation with dopamine in the presence of 1 microM haloperidol but not 1 microM sulpiride curtails the desensitization of dopamine-dependent adenylate cyclase. In dopamine-desensitized striatal slices of the Kd for N-propylnorapomorphine binding is increased but the content of membrane-bound calmodulin and the activation of adenylate cyclase by NaF and cholera toxin are decreased significantly. In striatal slices incubated with dopamine for prolonged time periods the coupling of the GTP-binding protein with adenylate cyclase and dopamine recognition sites may be impaired and the content of membrane-bound calmodulin is decreased.

Adenylyl Cyclases↗
PubMed1982

Symptomatological classification in the development of stroke in stroke-prone spontaneously hypertensive rats.

The developmental course of cerebrovascular diseases was examined by comparative neurological and pathological studies in stroke-prone SHR (SHRSP) which died spontaneously or were sacrificed. Behavioral status during their life span could be simply divided into 4 patterns, i.e., "no abnormalities", "irritable", "lethergic" and "akinetic" named Grades 0, I, II and III, respectively (Yamori's Classification). Grades I, II and III of behavioral status corresponded well to symptomato-pathoanatomically divided 3 stages (relating to brain edema), i.e., Stages I, II and III, respectively.

Animals↗
PubMed1982

Action of antihypertensive drugs in the central nervous system.

Several major antihypertensive agents appear to act by stimulating alpha receptors in the central nervous system. Other agents which lower blood pressure by peripheral mechanisms also have important central effects. Recent studies suggest that by enhancing norepinephrine turnover in the brain one can obtain a reduction in blood pressure in experimental animals. We have studied the enhancement of central norepinephrine turnover by tyrosine administration and by the antihypertensive agent Prazosin.

Animals↗
PubMed1982

Role of calmodulin in the activation of tryptophan hydroxylase.

Tryptophan hydroxylase can be activated 2.0- to 2.5-fold in vitro by ATPa dn Mg2+. This apparent phosphorylation effect is not dependent on cyclic nucleotides but is dependent on the presence of calcium. The activation of tryptophan hydroxylase by ATP-Mg2+ reduces the apparent Km of the enzyme for its cofactor, 6-methyltetrahydropterin, from 0.21 to 0.09 mM. The addition of certain antipsychotic drugs known to bind to calmodulin in a phosphorylation reaction mixture prevents the activation to tryptophan hydroxylase by ATP-Mg2+ in the concentration-dependent fashion. External addition of purified calmodulin protects the enzyme from the drug-induced effects. Preparation of calmodulin-free tryptophan hydroxylase by affinity chromatography on fluphenazine-Sepharose 4B yields an enzyme that is no longer activated by ATP-Mg2+, whereas the readdition of calmodulin to a calmodulin-free enzyme restores the responsiveness of tryptophan hydroxylase to ATP-Mg2+. This restoration is dependent on Ca2+. Taken together, these results indicate that the activation of tryptophan hydroxylase by phosphorylating conditions is dependent on both calcium and calmodulin.

Adenosine Triphosphate↗
PubMed1981

Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis.

The hydroxylase cofactor, tetrahydrobiopterin, and its biosynthetic system are localized in dopaminergic nerve terminals in the striatum. This conclusion is based on the nearly equivalent loss of tyrosine hydroxylase and tetrahydrobiopterin and its initial biosynthetic enzyme, guanosine triphosphate cyclohydrolase, after injection of 6-hydroxydopamine into the substantia nigra. The role of the hydroxylase cofactor in the regulation of dopamine synthesis is reassessed.

Aminohydrolases↗
PubMed1981

Pressor effects of dorsal raphe stimulation and intrahypothalamic application of serotonin in the spontaneously hypertensive rat.

Electrical stimulation of the dorsal raphe nucleus or direct microinjection of serotonin into the preoptic region of the anterior hypothalamus produces a transient rise in arterial blood pressure in both spontaneously hypertensive rats (SRH) and Wistar--Kyoto (WKY) controls. SRHs are more responsive to raphe stimulation but are somewhat less responsive to serotonin injections when compared to WKYs. The serotonin antagonist metergoline blocks the pressor response to serotonin in both strains. These results suggest that the central serotonergic neuronal system play a similar, but not identical, role in blood pressure modulation in hypertensive and normotensive rats.

Animals↗