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H Porzig

Publications and source records attributed to H Porzig.

At least 55 records · Page 3Linked to original sources
PubMed1983

[Beta-adrenergic receptors and plasma catecholamine behavior in trained and untrained athletes].

6 sports students (VO2 max. 54.0 +/- 2.6 ml/kg . min) and 6 marathoners (VO2 max. 65.7 +/- 2.0 ml/kg . min) performed graded treadmill tests. Free plasma catecholamines (noradrenaline and adrenaline), heart rate, lactate were assessed at rest and during exercise. The behaviour of beta-adrenergic receptors of polymorphonuclear leukocytes was estimated additionally before the treadmill test. The maximum running velocity was 14.6 +/- 0.8 km/h (sports students) and 17.3 +/- 0.6 km/h (marathoners). Noradrenaline was approximately 46% (v = 12 km/h) to 67% (v = 14 km/h) lower in the group of marathoners than in sports students; adrenaline showed no or smaller differences between both groups. No significant differences in the plasma catecholamine behaviour occurred between the groups at rest and during maximum exercise. Specific binding of 3H-Dihydroalprenolol to intact cells was higher in the marathoners than in sports students (p greater than 0.01). Scatchard analysis revealed a maximum binding of 21.1 fmol/10(7) cells (sports students) and 35.3 fmol/10(7) cells (marathoners), which indicated approximately 1,300 (sports students) and 2,150 binding sites cell (marathoners). Inverse correlations between noradrenaline (r = -0.63), VO2max. (r = -0.79) and the specific binding of 3H-DHA were observed. The reduction of plasma catecholamines (approximately 46-67%) and the increase in specific binding sites (approximately 67%) were in the same range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Determination of beta-receptors on intact polymorphonuclear leukocytes in autologous plasma].

The binding of tritium labelled radioligand dihydroalprenolol was investigated on live polymorphonuclear leukocytes of 6 endurance trained (VO2 max. 65.7 +/- 2.0 ml/kg . min), and 9 non-endurance trained subjects (VO2 max. 52.0 +/- 4.0 ml/kg . min). The specific binding of dihydroalprenolol is seen as an indicator of the beta-receptor density. The specific binding of dihydroalprenolol is defined as the difference between the total binding and that amount of dihydroalprenolol that could not be displaced. The leukocytes were reincubated for the binding studies in their autologous plasma. The specific binding of dihydroalprenolol on live polymorphonuclear leukocytes shows a levelling off behaviour at a concentration of approximately 2 nmol/l dihydroalprenolol in trained as well as in untrained subjects. The specific binding amounts to about 85% (0.1 nmol/l dihydroalprenolol) to 51% (2.0 nmol/l dihydroalprenolol) of the total binding. Based on Scatchard analysis, Bmax was determined as 41.2 fmol/10(7) cells (trained subjects) and 21.6 fmol/10(7) cells (untrained subjects). KD is 0.44 nmol/l dihydroalprenolol (untrained subjects), and 0.49 nmol/l dihydroalprenolol (trained subjects). The beta-adrenergic binding sites are approximately 1300 (untrained subjects), and 2500 binding sites/cell (trained subjects). The specific binding of dihydroalprenolol on live polymorphonuclear leukocytes is significantly higher in trained than in untrained subjects. This training dependent change in beta-receptor density may be an indicator of an increased sensitivity to catecholamines.

Alprenolol↗
PubMed1983

In vitro maturation of the rat reticulocyte beta-adrenoceptor adenylate cyclase system.

Reticulocytes but not mature erythrocytes are equipped with a functional beta-adrenergic system characterizing cells which are under adrenergic control. We have followed the decline of beta-adrenergic functions in a defined, phenylhydrazine-induced population of rat reticulocytes during maturation under cell culture conditions in vitro. beta-Agonist or forskolin-stimulated cyclic 3',5'-AMP (cAMP) formation decreased by 35 +/- 5% within 18 h and by 75 +/- 7% within 5 days. Regulatory control, i.e. the desensitization after chronic agonist exposure was observed at least for the first 18 h of incubation. The protein components of the system (receptors, nucleotide binding protein (N-protein), cyclase) seem to survive longer than 5 days. Our results suggest that an impaired interaction between N-protein and adenylate cyclase may be the initial step in the inactivation of the beta-adrenergic system in reticulocytes.

Adenylyl Cyclases↗
PubMed1982

Beta-adrenergic actions on cardiac cell membranes.

Adrenergic beta receptors are located on the heart cell surface membrane and can be identified directly by ligand-binding studies in intact cells. The maximal specific binding capacity of a labeled beta-adrenergic antagonist, [3H]-CGP, corresponds to about 6000 receptors per cell. Binding of adrenergic agonist results in changes in the membrane ion permeability for Ca which appears to involve an increase in the cAMP content of cardiac cells. Studies employing tracer methods and electrophysiological techniques suggest that the number of functional Ca channels in myocardium is regulated by beta-adrenergic receptors through the involvement of cAMP-mediated phosphorylation.

Adenylyl Cyclases↗
PubMed1982

Competitive and non-competitive interactions between specific ligands and beta-adrenoceptors in living cardiac cells.

We have used primary cultures of hearts from newborn rats to study beta-adrenoceptor properties in living myocardial cells. Receptors were labelled with the lipophilic antagonists 3H-(+/-)-carazolol and 125I-(+/-)-cyanopindolol (CYP) or with the hydrophilic antagonist 3H-(+/-)-CGP 12177. Under equilibrium conditions all ligands bound to a saturable homogeneous class of specific sites with a maximal binding capacity of approximately 100 fmol/mg protein (corresponding to approximately 5000 sites/cell). After 90-180 min preincubation of intact cells with 3H-carazolol or 3H-CGP 12177 only 80% of these antagonists could be displaced from specific binding sites by competing ligands. In the simultaneous presence of the antagonist (-) timolol 100% of specifically bound radiolabelled ligand remained displaceable. In competitive displacement experiments the radioligands did not affect the apparent affinity of the displacing nonlabelled antagonists timolol and CGP 12177, but agonist affinity was markedly changed. The apparent KD values for (-)-isoprenaline were 1560 and 2720 nmol/l in the presence of carazolol and CYP, but only 32 nmol/l in the presence of CGP 12177. This antagonist-dependent difference in agonist KD values was observed only in intact cells but not in membrane particles prepared from heart homogenates of newborn rats, where high agonist affinity was seen during displacement of all radioligands. The KA value for isoprenaline-stimulated cAMP accumulation in living cells was 30 nmol/l in 5-day cultures. A direct proportionality existed between agonist receptor occupation and cAMP accumulation in the presence of CGP 12177 as estimated by the KA/KD ratio. In the presence of carazolol the KA/KD ratio decreased from 1 to 0.02 suggesting that low affinity receptors were not coupled functionally to adenylate cyclase. These results indicate that some lipophilic antagonists which appear to be inert competitive ligands in fragmented membranes, alter receptor binding properties in intact cells. These antagonists seem to promote the transformation of receptor sites into a new "inactivated" state where competitive interactions between different ligands are inhibited.

Animals↗
PubMed1981

Quantitative changes in beta-adrenergic responses of isolated atria from hyper- and hypothyroid rats.

Concentration-response curves for the chronotropic and inotropic effects of isoprenaline, in the absence and presence of propranolol, were obtained on heart atria isolated from normo- or dysthyroid rats. Hyperthyroidism increased the chronotropic potency and efficacy of the beta-adrenergic agonist. The results are compatible with the view that thyroid hormone increases the density of functional beta-adrenoceptors in cardiac pacemaker tissue.

Animals↗
PubMed1981

Beta-adrenergic receptors and responses in the heart.

This article summarizes some essential steps leading to one of the most prominent beta-adrenergic effects on the heart, the increase in force of contraction. Binding of beta-adrenergic agonists and antagonists, activation of the enzyme adenylate cyclase by agonist binding, increase in membrane permeability to calcium ions, possibly via cyclic AMP, and increase in force of contraction and its relation to enhanced calcium influx are briefly discussed.

Action Potentials↗
PubMed1980

The effects of Ca2+ and guanylnucleotides on isoprenaline-stimulated cyclic AMP formation in rat reticulocyte ghosts.

We have studied beta-adrenergic stimulation of cyclic AMP formation in fragmented membranes and in unsealed or resealed ghosts prepared from rat reticulocytes. The maximal rate of isoprenaline-stimulated cyclic AMP formation with saturating MgATP concentrations and in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine was 5-8 nmol/min per ml ghosts and remained constant for at least 15 min. Transition from resealed ghosts to fragmented membranes was associated with a shift of the activation constant (Ka) for (+/-)-isoprenaline from 0.1 to 0.6 microM. THe apparent dissociation constant for propranolol (0.01 microM) remained unchanged. The Ka values for isoprenaline in native reticulocytes and in resealed ghosts were identical. The stimulating effect of NaF on cyclic AMP formation in resealed ghosts reached 15% of maximal beta-adrenergic stimulation. Cyclic AMP formation, both in fragmented membranes and in ghosts, was half-maximally inhibited with Ca2+ concentrations ranging between 0.1 and 1 microM. GTP stimulated isoprenaline-dependent cyclic AMP formation in unsealed ghosts and in fragmented reticulocyte membranes by a factor of 3-5 but did not change the Ka value for isoprenaline. Ka values for the guanylnucleotides in different experiments varied between 0.3 and 2 microM. Ca2+ concentrations up to 4.6 microM reduced the maximal activation by GTP and Gpp(NH)p but did not affect their Ka values. Compared to GTP, maximal activation by Gpp(NH)p was higher in fragmented membranes, but much lower in ghosts. Our results suggest that the native beta-receptor adenylate cyclase system of reticulocytes is more closely approximated in the ghost model than in fragmented membrane preparations. Membrane properties seem to modulate the actions of guanylnucleotides on isoprenaline-dependent cyclic AMP formation in ghosts. Some of these effects are not observed in isolated membranes.

Adenylyl Cyclases↗
PubMed1977

Studies on the cation permeability of human red cell ghosts. Characterization and biological significance of two membrane sites with high affinities for Ca.

Net K movements in reconstituted human red cell ghosts and the resealing of ghosts to cations after osmotic hemolysis of red cells have been studied as functions of the free Ca ion concentration. The Ca-dependent specific increase in K permeability was shown to be mediated by a site close to the internal surface of the membrane with an apparent dissociation constant ap pH 7.2 for Ca (K'p1) of 3-5 X 10(-7) M, for Sr of 7 X 10(-6) M. Ba and Mg did not increase the K-permeability of the membrane but inhibited the Ca-mediated permeability changes. K'D1 decreased in a nonlinear fashion when the pH was increased from 6.0 to 8.5. Two different pK' values of this membrane site were found at pH 8.3 and 6.3. The Ca-activated net K efflux into a K-free medium was almost completely inhibited by an increase in intracellular Na from 4 to 70mM. Extracellular K antagonized this Na effect. Changes in the extracellular Na (0.1-140 mM) or K (0.1-6 mM) concentrations had little effect and did not change K'p1. The Ca-stimulated recovery of a low cation permeability in ghost cells appeared to be mediated by a second membrane site which was accessible to divalent cations only during the process of hemolysis in media of low ionic strength. The apparent dissociation constant for Ca at this site (K'p2) varied between 6 X 10(-7) and 4 X 10(-6) M at pH 7.2 Mg, Sr, and Ba could replace Ca functionally. The selectivity sequence was Ca greater than Sr greater than Ba greater than Mg. K'p2 was independent on the pH value in the range between 6.0 and 8.0 Hill coefficients of 2 were observed for the interaction of Ca with both membrane sites suggesting that more than one Ca ion is bound per site. The Hill cofficients were affected neither by the ion composition nor by the Ph values of the intra-and extracellular media. It is concluded that two different pathways for the permeation of cations across the membrane are controlled by membrane sites with high affinities for Ca: One specific for K, one unspecific with respect to cations. The K-specific "channel" has properties similar to the K channel in excitable tissues.

Calcium↗
PubMed1975

The effect of substances releasing intracellular calcium ions on sodium-dependent calcium efflux from guinea-pig auricles.

1. 45-Ca efflux and resting tension were measured in isolated guinea-pig auricles under conditions known to change the intracellular free Ca ion concentration. 2. In the presence of [Na]o, caffeine (2mM) increases 45-Ca efflux, but does not produce a contracture, while in the absence of [Na]o and [Ca]o caffeine causes a contracture without increasing 45-Ca efflux. Adrenaline (10-minus5-10-minus 4M) with or without theophylline (0-5-1-0mM) has no effect on either 45-Ca efflux or resting tension. 3. In the presence of caffeine the rate of net efflux of Ca depends on [Na]o-2. Caffeine contractures of muscles in Na-free solution relax upon the addition of [Na]o. Relaxation is correlated with the increase in net efflux of Ca. 4. Cyanide (2mM) produces a variable increase in 45-Ca efflux without a concomitant contracture in Na-containing solutions, but in Na, Ca-free solutions a large contracture occurs without significant increase in 45-Ca efflux. 5. A large increase in 45-Ca efflux and a contracture were observed with the 'Ca-ionophore' X 537 A. 6. Changes in membrane potential (K-depolarization) in hypertonic solutions have no significant effect on Na-dependent 45-Ca efflux, which is an agreement with an electroneutral 2:1 Na-Ca exchange. 7. Cyanide and X 537 A both cause a considerable release of Ca ions from isolated guinea-pig heart mitochondria, while caffeine has no effect. 8. The results suggest a powerful role of the Na-Ca exchange system in reducing the intracellular Ca concentration after Ca release from intracellular stores.

Animals↗
PubMed1975

Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts.

1. The effects of two positively charged local anaesthetic amines, tetracaine and propranolol, on cation permeability were studied in resealed human red cell ghosts prepared from metabolically depleted erythrocytes. 2. The K permeability was reduced by tetracaine but increased by propranolol. The effect of tetracaine was independent of extracellular Ca concentration but was raised to 2-5 x 10(-7) M. The effect of propranolol, which was enhanced when the external Ca concentration was raised, could be completely inhibited by lowering the internal free Ca to less than 10(-7) M. 3. Propranolol, but not tetracaine, increased the intracellular Ca ion concentration by releasing up to 20% of the membrane-bound Ca to the cell interior. This increase in intracellular Ca was sufficient to mediate the observed change in K permeability. 4. Tetracaine and propranolol reduced the Ca binding capacity of the ghost membrane by about 20 and 40% respectively. The Ca permeability was increased by propranolol and was slightly reduced by tetracaine. 5. In high concentrations (2-7 mM) propranolol by itself moderately increased K and Na permeability, but supressed completely the Ca-induced increase in K permeability. Tetracaine in concentrations up to 4 mM enhanced the Ca-induced increase in K permeability. Higher concentrations of the drug caused lysis of the cells. 6. Maximally effective concentrations of tetracaine and propranolol inhibited the ATP-dependent Ca outward transport by 30 and 70% respectively. 7. The effects of tetracaine on K permeability were shared by the local anaesthetics prilocaine and lidocaine, those of propranolol were shared by practolol, a beta-adrenergic antagonist and tetraethylammonium, a ganglionic blocking agent. 8. It is suggested that the differences in the effects of tetracaine and propranolol on cation permeability reflect qualitatively different interactions of the two drugs with Ca binding sites on the inner surface of the membrane.

Adenosine Triphosphate↗