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Biomedical subjects

K Mohr

Publications and source records attributed to K Mohr.

At least 91 records · Page 5Linked to original sources
PubMed1988

Interpretation of [3H]ouabain binding in guinea-pig ventricular myocardium in relation to sodium pump activity.

1. The attempt was made to analyse the complex [3H]ouabain binding curves obtained in intact cardiac ventricular preparations electrically stimulated at different frequencies. The result of this analysis was used to draw conclusions from the binding curves on the frequency dependence of sodium pump activity. 2. [3H]Ouabain binding to isolated, electrically stimulated (1.5 Hz) ventricular strips of guinea-pig hearts was investigated. The positive inotropic effects were studied in separate experiments. Specific [3H]ouabain binding barely reached an equilibrium within 3 h of incubation. A binding curve was constructed using the equilibrium values of specific [3H]ouabain binding obtained at different ouabain concentrations. This binding curve revealed a concentration-proportional component at positive inotropic concentrations and a saturating component at high, toxic concentrations. At very low, inotropically ineffective ouabain concentrations, however, binding values were higher than expected from a linear relationship between ouabain concentration and binding. 3. The peculiar shape of the binding curve could be largely accounted for by a mathematical model, which takes into consideration biochemical properties and physiological regulation of the sodium pump. The model predicts a concentration-proportional pattern of binding which takes place in the non-toxic ouabain concentration range. The slope of the concentration-proportional component of the binding curve should represent a measure of sodium pump activity. 4. Investigation of binding curves at various stimulation frequencies revealed that, as predicted by the model, the slope of the concentration-proportional component of the binding curves was increased and the maximum non-toxic equilibrium binding was decreased with increasing beat frequencies. 5. Quantitative evaluation of the binding curves led to the conclusion that sodium pump activity is a linear function of stimulation frequency in guinea-pig ventricular preparations, the activity in resting preparations amounting to about 15% of the maximum activity. Comparison of the present results with former studies on sodium pump function suggests that [3H]ouabain binding reflects steady-state sodium pump activity. If the complex pattern of binding curves is taken into consideration, [3H]ouabain binding measurements may serve as a means of studying sodium pump function.

Animals↗
PubMed1988

Release of N-[3H]methylscopolamine from isolated guinea pig atria is controlled by diffusion and rebinding.

This study attempts to analyze the inter-relationship between the slow fading of muscarinic antagonist action observed in isolated tissue preparations upon washout and the dissociation kinetics at the receptor level. Isolated guinea pig left atria stimulated electrically at 3 Hz were equilibrated with N-[3H]methylscopolamine ([3H]NMS) and the time course of release of [3H]NMS was studied. In parallel experiments, the fading of the antimuscarinic action of NMS was monitored by repeated determinations of the negative inotropic effect of oxotremorine. In comparison, the dissociation of [3H]NMS from muscarinic receptors was recorded in a membrane suspension of guinea pig right atria. Having been equilibrated at 10(-8) M [3H]NMS, the atria released [3H]NMS extremely slowly, when transferred into a drug-free washout bath: not even half of the initially bound [3H]NMS was lost within 3 hr. With a corresponding time course, 10(-8) M oxotremorine regained its negative inotropic action. In contrast, when 10(-4) M unlabeled NMS was present in the washout bath, it took only 5 min for the [3H]NMS binding to fall by 50%. Similarly, in a membrane-suspension of guinea pig right atria, the half-life time of the [3H]NMS receptor complexes amounted to about 5 min. It is concluded that the dissociation of NMS from its receptor sites proceeds with a half-life time of 5 min in intact atria as well as in the cardiac membrane suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Acrihellin, a cardioactive steroid escaping from the organ-bath.

The concentration of acrihellin rapidly declines in oxygenated Tyrode-solution, because the compound escapes from the organ-bath being enriched in droplets sprayed from the surface of the bubbled solution. As checked by radiochromatography, acrihellin remains chemically unaltered during this process. Hellebrin and hellebrigenin persist in gassed Tyrode-solution, suggesting that the 3 beta-substituent dimethylacrylic acid endows acrihellin with amphiphilic properties, thus promoting its enrichment at gas-water interphases. Measurements of the inotropic effects in guinea pig left atria performed at concentrations of acrihellin kept constant yielded a dose-response curve, which closely resembles that of the conventional cardioactive steroid ouabain.

Animals↗
PubMed1987

High and concentration-proportional accumulation of [3H]-nitrendipine by intact cardiac tissue.

The binding of [3H]-nitrendipine to intact, electrically driven isolated left atria of guinea-pigs was investigated over the concentration range 10(-10) M to 3 X 10(-5) M. A high affinity binding site saturable in the nM range as found in ventricular homogenates could not be detected. Instead the accumulation of nitrendipine in intact atria was found to be proportional to the concentration from 10(-10) M to 10(-6) M; beyond 10(-6) M the binding started to become saturated. Nitrendipine was highly accumulated in atrial tissue. The cell:medium ratios amounted to about 120 in the range from 10(-10) M to 10(-6) M. The concentration-response curve for the negative inotropic action of nitrendipine yielded an ED50 of 3 X 10(-7) M, thus lying within the range of concentration-proportional accumulation. The reduction of the contractile force proceeded faster (t1/2 less than 10 min) than the uptake process t1/2 approximately 40 min) suggesting that it is the binding of nitrendipine into a superficial compartment, which interferes with the excitation-contraction coupling. The results suggest that the high concentration of nitrendipine present in hydrophobic cellular compartments such as the plasmalemma might be involved in its pharmacological action.

Animals↗
PubMed1986

Light and electron microscopical morphometry of pituitary adenomas in hyperprolactinemia.

Two highly differentiated acidophil prolactin-cell adenomas with hyperprolactinemia (group I), 8 large cell chromophobe adenomas with hyperprolactinemia (group II), and 2 small cell chromophobe adenomas (group III), one of which was combined with hyperprolactinemia, were studied immunohistologically. Morphometry was performed on the light- and electron microscopical level. The 11 active adenomas were immunohistologically positive for prolactin, the 12th adenoma with normal prolactin plasma level was negative for prolactin. Light microscopical morphometry displayed significantly more cells of smaller size in the "small cell chromophobe" adenomas, whereas the large cell chromophobe adenomas and the highly differentiated prolactin cell adenomas were not different. Ultrastructural morphometry demonstrated significant differences between highly differentiated prolactin cell adenomas (group I), and large cell chromophobe adenomas (group II). The latter contain smaller "relative volumes" of nucleoli and of secretory granules, whereas the rough endoplasmic reticulum, the Golgi fields and the nuclei were not different. Comparison of large cell chromophobe adenomas (group II), and small cell chromophobe adenomas (group III) revealed significantly larger relative volumes of nuclei and of mitochondria but smaller volumes of rough endoplasmic reticulum and of Golgi fields in the small cell chromophobe adenomas. Significant differences between the active and the inactive adenoma of small cell chromophobe type in the group III were not found. In spite of the low quantity of small cell chromophobe adenomas and of acidophil prolactin cell adenomas, our data demonstrate that there exist distinct and significant light microscopical and ultrastructural differences between the three adenoma types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Acidophil↗
PubMed1985

On the cooperativity of ouabain-binding to intact myocardium.

A theoretical concept is presented which proposes that binding of ouabain to intact myocardium should be positive cooperative. It is based on the assumption that the myocardial Na/K-ATPases expose the ouabain-binding site only at a particular conformation adopted during a turnover cycle. The turnover rate and thus the ouabain-binding properties are regulated by the cytosolic Na-ion-concentration Nai. Any occupation of cellular Na/K-ATPases should affect the ouabain-binding properties of the unoccupied Na/K-ATPases, because their turnover rate is increased via an elevated Nai. A computer model which takes into account the interrelationships of the Na/K-ATPases both with Nai and with the ouabain-concentration predicts that ouabain-binding should proceed in a concentration-proportional fashion as long as the Na-load can be counterbalanced by non-occupied Na/K-ATPase molecules. The concentration-proportional binding reflects a positive cooperativity. Experimental results reveal that (3H)ouabain-binding to Na/K-ATPase of electrically stimulated guinea-pig left atria was in fact concentration-proportional under certain experimental conditions. The biological significance of the proposed concept remains to be elucidated.

Animals↗
PubMed1985

Sodium load and high affinity ouabain binding in rat and guinea-pig cardiac tissue.

An estimation of the actual Na/K-ATPase transport activity in intact cardiac cells was made by measuring the binding of [3H]-ouabain to rat and guinea-pig ventricular strips. At the low [3H]-ouabain concentration of 1 nM equilibrium binding was hardly obtained after an incubation time of five hours. Different procedures known to alter the sodium load of the cardiac preparations influenced [3H]-ouabain binding: the sodium ionophore monensin enhanced [3H]-ouabain binding, the local anaesthetic dibucaine and a reduction of external sodium ion concentration diminished [3H]-ouabain binding; [3H]-ouabain binding was similarly affected by these procedures in the rat and guinea-pig. Since [3H]-ouabain binding occurred predominantly at the high-affinity binding sites of rat myocardium under the applied experimental conditions, it was concluded that these binding sites represent Na/K-ATPase molecules involved in sodium ion transport.

Animals↗
PubMed1984

Action of ouabain on rat heart: comparison with its effect on guinea-pig heart.

The inotropic dose-response curve of ouabain in rat cardiac ventricular strips exceeded a concentration range of two decades (1 X 10(-7) M to 3 X 10(-5) M) displaying an intermediate plateau phase. In guinea-pig ventricular strips the inotropic ouabain concentrations spanned only one decade (1 X 10(-7) M-1 X 10(-6) M). Ouabain-intoxication in guinea-pig ventricular strips occurring at 3 X 10(-6) M consisted of arrhythmia and contracture, while in rat ventricular strips at the toxic concentration of 1 X 10(-4) M only a progressive increase in diastolic tension was observed. By means of atomic absorption spectroscopy the ouabain-induced loss of cellular potassium and gain of sodium in rat ventricular strips was detected only at concentrations of ouabain higher than 10(-4) M. Ouabain reduced the activity of Na/K-ATPase prepared from rat and guinea-pig cardiac ventricles to half of its maximum at 6.5 X 10(-5) M in rat and 1.0 X 10(-6) M in guinea-pig, rat heart Na/K-ATPase thus being about 60 fold less sensitive towards ouabain. Specific [3H]-ouabain binding to membrane suspensions prepared from rat and guinea-pig ventricles was characterized by a similar affinity in rat (KD = 4 X 10(-8) M) and guinea-pig (KD = 13 X 10(-8) M). The number of ouabain binding sites in rat membranes was only about 10% of the number found in guinea-pig membranes. In rat the presence of additional ouabain-binding with low affinity and high capacity seemed possible, but could not be verified for methodological reasons. In the light of the biochemical results and binding data, the wider range of ouabain concentration exerting a positive inotropic effect in the rat may be attributed to the existence in the latter of two populations of receptors with different affinities for ouabain and different capacities. In contrast, in the guinea-pig, there is a single population. Nevertheless it is probable that all the receptors in both species are part of the Na/K-ATPase complex and mediate a positive inotropic effect after ouabain-binding in an identical manner.

Animals↗
PubMed1983

Influence of various cationic amphiphilic drugs on the phase-transition temperature of phosphatidylcholine liposomes.

The influence of 16 cationic amphiphilic compounds from various pharmacological groups on the phase-transition temperature (Tt) of dipalmitoyl-phosphatidylcholine (DPPC) liposomes was investigated using the method of differential scanning calorimetry. All drugs, the hydrophobicity of which varied in a wide range, depressed Tt. Biphasic dose-effect curves were obtained when the reduction of Tt (delta Tt) was plotted vs the molar ratio of drug/DPPC; beyond a plateau, Tt could again be reduced markedly by increasing the molar ratio. Concomitantly with the depression of Tt, the width of the transition peak changed in a characteristic way: it broadened during the (first) steep part of the dose-effect curves and became narrow like a control transition when the plateau of the dose-effect curves was reached. At still higher ratios the peak broadened again and eventually vanished, probably due to a detergent-like effect of the drug. Increasing hydrophobicity of the compounds shifted the dose-effect curves to lower molar ratios and enhanced the delta Tt attained at the plateau phase. It is proposed that the different potencies of the drugs to depress Tt result from different binding equilibria between the compounds and DPPC membranes, the individual equilibrium being determined by hydrophobic attraction and electrostatic repulsion.

Anions↗
PubMed1983

Influence of cationic amphiphilic drugs on the characteristics of ouabain-binding to cardiac Na+/K+-ATPase.

The influence of 12 cationic amphiphilic compounds on the equilibrium and kinetic characteristics of the binding of tritium-labelled ouabain to the lipoprotein Na+/K+-ATPase present in a crude membrane suspension of guinea pig myocardium was investigated. The drugs, e.g. local anaesthetic, antiarrhythmic and psychotropic agents, inhibited specific binding of ouabain in a concentration-dependent manner by reducing its affinity without affecting the number of binding sites. In the presence of chlorpromazine, propranolol and dibucaine, the decreased affinity of ouabain was due to both a diminished association rate and an increased dissociation rate, while in the presence of the weakly potent procaine only the association rate of ouabain was found to be reduced. The different potency of the catamphiphilic drugs was well correlated to the degree of their hydrophobicity. Evidence is presented that the protonized form of the drugs is the effective one. Concerning the mode of action, the catamphiphilic drugs are proposed to interact with the phospholipid part of the lipoprotein Na+/K+-ATPase, thereby indirectly altering the conformation of the embedded protein moiety and thus reducing the proper fit between ouabain and its receptor.

Animals↗
PubMed1982

On the binding of a 3-alpha-methylated digitoxigenin-glucoside to ouabain receptors in heart muscle homogenate.

3-alpha-Methyl substituted digitoxigenin-3-beta-glucoside (methyl-dtg-gluc) displays unusual features, e.g. a high dissociation rate constant from its binding site leading to rapid reversibility of the inotropic and toxic effects, and a flat dose-response curve attaining higher inotropic maxima thus indicating an increased therapeutic index in animal experiments. In order to check whether or not methyl-dtg-gluc is specifically bound to the same receptors as classic cardiac glycosides we compared binding of ouabain and of methyl-dtg-gluc to guinea-pig heart muscle homogenate. For both compounds specific binding required the addition of ATP (2.5 mM). The binding curve for ouabain yielded half maximum binding at 1.3 x 10(-7) M and maximum number of binding sites of 6 pmole/mg protein; the corresponding values for methyl-dtg-gluc amounted to 1.4 x 10(-6) M and 6 pmole/mg protein, respectively. A mutual competition could be demonstrated between the two compounds. Since the provided data are equilibrium values they do not exclude higher turnover rates of methyl-dtg-gluc in comparison with ouabain at a given glycoside-ATPase complex concentration which can be expected from the fast dissociation rate constant of the methyl-dtg-gluc-ATPase complex. The results are briefly discussed with respect to the molecular mole of action of cardiac glycosides.

Animals↗
PubMed1982

Adrenocortical function of rats under prolonged administration of lipidosis-inducing drugs.

The influence of three potent lipidosis-inducing agents, i.e. iprindole, triparanol and chloroquine, on the rat adrenal cortex was investigated by determination of the corticosterone excretion in the urine, the responsiveness to ACTH and by determination of the corticosterone content of the adrenals and of the corticosterone concentration in plasma. Administration of iprindole and triparanol left the function of the adrenal cortex unaffected, while under chloroquine treatment an activation with time was observed. Morphologically, similar degrees of lipidosis were found in all experiments. The results demonstrate that the functional capacity of the rat adrenal cortex is not directly correlated to lipidotic alterations.

Adrenal Cortex↗
PubMed1982

The effect of indomethacin on spontaneous and human menopausal gonadotropin induced pressure changes in the tissue and arterial vascular system from human ovaries perfused in vitro.

Eight human ovaries were perfused in a closed recirculating system with a semisynthetic, hemoglobin-free medium. Arterial and intraovarian pressures were recorded simultaneously. In three experiments spontaneous pressure changes were noticed. In five experiments pressure changes were induced with human menopausal gonadotropin (hMG) (approximately 70mIU/ml follicle stimulating hormone (FSH) and 40mIU/ml luteotrophic hormone (LH) II. IRP-hMG). Frequency and amplitude of pressure changes in the arterial system and fluctuations in tissue pressure were reduced with indomethacin (20 micrograms/ml). In one experiment 40 micrograms/ml indomethacin had been used. In spite of the high dose of indomethacin arterial and tissue pressure changes were not abolished in all experiments. Therefore it is assumed that vascular and tissue activities are not mediated by prostaglandins only.

Adult↗
PubMed1980

[Angiographic diagnosis of subarachnoid hemorrhage--a study of 160 patients].

Among 1916 cerebral angiographies carried out in the years 1973 to 1977, the examination was made in 160 patients (= 8.4 per cent) after verified subarachnoid haemorrhages. In 107 cases (= 67 per cent) a morphological substrate was secured angiographically. Arterial cerebral aneurisms and arteriovenous angiomas were the most frequent causes of a haemorrhage with an occurrence of 32.5 and 16.3 per cent, respectively. Further causes were: degenerative diseases of the cerebral vessels in 11.9 per cent, intracerebral haematomas in 3.1 per cent, haemorrhages in tumours in 1.9 per cent and stenosis of the aortic isthmus in 1.3 per cent of the cases. In 33 per cent of the cases a morphological substrate could not be ascertained angiographically. Including the authors' own experiences, diagnostic criteria are derived which to a large extent co-determine the decision with regard to an operation including the respective technical procedure.

Adult↗