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G Wiemer

Publications and source records attributed to G Wiemer.

68 records · Page 4Linked to original sources
PubMed1979

Inversal relationship between basal adenylcyclase activity and maximal degree of stimulation in membranes of red blood cells from rats.

The degree of stimulation of adenylcyclase activity, in membranes from immature red blood cells from rats, brought about by isoprenaline, guanylyl-imidodiphosphate and sodium fluoride is strongly dependent on the basal activity of the enzyme. The inversal relationship between basal activity and the maximal degree of stimulation by (--) isoprenaline, shows an apparent seasonal dependence.

Adenylyl Cyclases↗
PubMed1978

Direct characterization of beta-adrenoceptors in membranes of immature red blood cells from rats.

By means of the radioactive antagonist ligand (3H)(-) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized as beta-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temperature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited by beta-adrenergic antagonists (pindolol greater than alprenolol greater than or equal to propranolol greater than practolol) and agonists (isoprenaline greater than adrenaline). The (-) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80% treatment of the animals with increasing doses of acetyl phenylhydrazine.

Alprenolol↗
PubMed1978

Correlation between isoprenaline-stimulated synthesis of cyclic AMP and occurrence of beta-adrenoreceptors in immature erythrocytes from rats.

When increasing reticulocytosis (up to 80%) was induced in rats by treatment with acetyl-phenylhydrazine (up to 70 mg/kg on 3 consecutive days) synthesis of cAMP stimulated by isoprenaline in intact red blood cells and in the related membrane preparations increased up to 100-fold. At the same time the density of beta-adrenoreceptor sites (measured by ligand binding with (3H)(-)-dihydroalprenolol) in the related membrane preparations was only increased about 5-fold. There was however a linear correlation between the increase of isoprenaline-stimulated enzyme activity and the receptor density in membrane preparations. The results indicate that mature red cells contain beta-adrenoreceptor sites but little or not adenyl cyclase activity. Thus, during the maturation process of these cells, enzyme activity and receptor densities decrease at different speeds indicating a different turnover of these two entities of the cytoplasmic membrane.

Adenylyl Cyclases↗
PubMed1978

Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity. Evidence for a metallic site.

In membrane preparations from immature erythrocytes from rats the effects of the divalent cations Mg2+, Mn2+ and Ca2+ on basal activity of adenylcyclase as well as on enzyme activity stimulated by isoprenaline (Ipn) or guanylyl-imidodiphosphate [Gpp(NH)p] were investigated.--Mn2+ is a ten-fold stronger activator of the enzyme than Mg2+ irrespective of the stimulant used. At suboptimal concentrations of the cations at all concentrations of Gpp(NH)p used (10(-6) to 10(-3) M) reaction velocities increase progressively over an incubation period of 40 min. Optimal cation concentrations, however, i.e. 3 x 10(-3) M Mn2+ and 3 x 10(-2)M Mg2+ elicit a constant and at 10(-4) M Gpp(NH)p maximal reaction velocity. In contrast, the Ipn-stimulated cAMP synthesis proceeds linearly at all Ipn concentrations used; a change of cation concentrations elicits only a change in reaction velocity, which is maximal at 10(-3) M Mn2+ and 10(-2) M Mg2+ respectively.--Ca2+ inhibits adenylcyclase activity in a non-competitive manner, irrespective of the stimulant and ion concentration used. The Mg2+-activated enzyme, however, is more susceptible to the inhibiting effect of Ca2+ than the Mn2+-activated enzyme.--It is concluded that Mn2+ and Mg2+ are allosteric effectors of the enzyme adenylcyclase, acting at a Me2+-site of the catalytic unit of adenylcyclase.

Adenosine Triphosphate↗
PubMedDate not supplied

Angiotensin converting enzyme inhibitors, left ventricular hypertrophy and fibrosis.

From pharmacological investigations and clinical studies, it is known that angiotensin converting enzyme (ACE) inhibitors exhibit additional local actions, which are not related to hemodynamic changes and which cannot be explained only by interference with the renin angiotensin system (RAS) by means of an inhibition of angiotensin II (ANG II) formation. Since ACE is identical to kininase II, which inactivates the nonapeptide bradykinin (BK) and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. a) In rats made hypertensive by aortic banding, the effect of ramipril in left ventricular hypertrophy (LVH) was investigated. Ramipril in the antihypertensive dose of 1 mg/kg/day for 6 weeks prevented the increase in blood pressure and the development of LVH. The low dose of ramipril (10 micrograms/kg/day for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity but also prevented LVH after aortic banding. The antihypertrophic effect of the higher and lower doses of ramipril, as well as the antihypertensive action of the higher dose of ramipril, was abolished by coadministration of the kinin receptor antagonist icatibant. In the regression study the antihypertrophic actions of ramipril were not blocked by the kinin receptor antagonist. Chronic administration of BK had similar beneficial effects in a prevention study which were abolished by icatibant and NG-nitro-L-arginine (L-NNA). In a one year study the high and low dose of ramipril prevented LVH and fibrosis. Ramipril had an early direct effect in hypertensive rats on the mRNA expression for myocardial collagen I and III, unrelated to its blood pressure lowering effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Neurochemical effects of the synthetic ACTH4-9-analog Hoe 427 (Ebiratide) in rat brain.

The ACTH4-9-analog Hoe 427 systemically injected in a dose range from 0.01-10 micrograms/kg caused a fall in acetylcholine (ACh) content in different brain areas of the rat. This effect occurred 0.5 hour after a single administration and lasted up to 24 hours. The decrease in ACh content induced by Hoe 427 was more pronounced when the animals were pretreated with dexamethasone (over 7 days 1 mg/kg SC, daily). Coadministration of the choline uptake inhibitor hemicholinium-3 (HC-3) and Hoe 427 potentiated the decrease in ACh content induced by HC-3. In the same dose range Hoe 427 acutely evoked an increase of the activity of the enzyme choline acetyltransferase as well as an elevation of brain cyclic GMP content. These data indicate that Hoe 427 enhances ACh metabolism in rat brain after systemic administration.

Acetylcholine↗
PubMedDate not supplied

Learning and memory processes of an ACTH4-9 analog (ebiratide; Hoe 427) in mice and rats.

These experiments investigated the effects of the new ACTH4-9 analog ebiratide (Hoe 427) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH-(CH2)8-NH2 X 3 CH3COOH] on memory processes in mice and rats in five training tasks. With all five training and testing procedures (inhibitory avoidance test with ECS- or scopolamine-induced amnesia, up-hill avoidance, one-way shuttle box avoidance and eight-arm radial maze) ebiratide was most effective in a dose range of 1-10 micrograms/kg SC.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Increase of Bmax-values of beta-adrenoceptor sites after chronic treatment with reserpine?

After treatment of rats with 5 x 0.5 mg/kg/d reserpine in membrane preparations from the parotid gland no increase in the total number of beta-adrenoceptors (Bmax) was observed using the antagonist ligand (-)3H-dihydroalprenolol. There occurred, however, a pronounced increase of the high affinity agonist binding component. Thus, it appears that not the absolute number of beta-adrenoceptor sites but the relative amount of high affinity sites is most sensitive against the sensitization process. The results are in contrast to those of other authors. We suspect that increases of Bmax-values after reserpine can be simulated by the loss of noradrenaline whereas in control membranes noradrenaline is still bound to the adrenoceptors thus preventing the radioactive ligand from access to these sites. We highly recommend to use preincubation methods prior to ligand binding studies in order to remove endogenous ligands still bound to the high affinity site of the beta-adrenoceptor.

Animals↗