PubMed Health⌕ Search

Biomedical subjects

R Ortmann

Publications and source records attributed to R Ortmann.

52 records · Page 3Linked to original sources
PubMed1977

Stimulation of adenosine 3':5'-monophosphate formation by prostaglandins in human astrocytoma cells. Inhibition by nonsteroidal anti-inflammatory agents.

Prostaglandins (PG) of the E series and catecholamines stimulate adenosine 3':5'-monophosphate (cAMP) formation in human astrocytoma cells (1321N1). These two classes of effectors activated adenylate cyclase upon interaction with different receptor systems. No evidence for a mediatory role for PG in the action of catecholamines was found. PG interacted with 1321N1 cells with an order of potency of PGE1 = PGE2 greater than PGA1 greater than PGF2 alpha. The effect of combinations of the various PG indicated that all efficacious PG interacted with a common receptor. 7-Oxa-13-prostynoic acid and indomethacin were shown to be competitive inhibitors of the effect of PGE1 with Ki values of 4 and 150 micron, respectively. These two compounds did not inhibit the effect of isoproterenol. Polyphloretin phosphate caused a complex pattern of inhibition of the effects of PGE1 and at higher concentrations also inhibited the effects of isoproterenol. The mefenamate class of nonsteroidal anti-inflammatory agents was found to inhibit the effects of PGE1 with a potency order of meclofenamic acid greater than flufenamic acid = mefenamic acid. The inhibitory action of meclofenamic acid was complex involving specific, but partial, insurmountable antagonism of PGE1 as well as competitive inhibition of PGE1 effects. At higher concentrations of meclofenamic acid a nonspecific inhibition of the effects of both PGE1 and isoproterenol was observed. These studies suggest that the inhibition by nonsteroidal anti-inflammatory agents of the physiological effects of PGE1 in animals may occur, at least in part, at the level of adenylate cyclase. The possibility that multiple classes of adenylate cyclase-linked PGE receptors might exist in nature is discussed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1976

Growth of astrocytoma cells in the presence of prostaglandin E1: effect on the regulation of cyclic AMP metabolism.

Human astrocytoma cells (1321N1) in culture respond to pharmacological concentrations of prostaglandins and catecholamines with a marked increase in the accumulation of cyclic AMP. However, growth of 1321N1 cells in the presence of low concentrations (0.003 to 0.1 muM) of prostaglandin E1 (PGE1) results in a marked reduction in the responsiveness of the cells-even to concentrations of PGE1 that normally stimulate maximal accumulation of cyclic AMP. Occasionally, a partial reduction in the responsiveness to catecholamines was observed in cells grown in the presence of PGE1. When it occurred this effect could be correlated with an increase in the cyclic AMP-degradation capacity of the cells. This loss of responsiveness to catecholamines could be completely reversed by 1-methyl-3-isobutylxanthine, a potent inhibitor of phosphodiesterase activity in 1321N1 cells. The consistently observed and more profound desensitization to the effects of PGE1 could not be correlated with an increase in cyclic AM-degradative capacity. Accordingly, 1-methyl-3-isobutylxanthine was only minimally effective in reversing desensitization to PGE1. It is concluded that the inability of 1321N1 cells grown in the presence of PGE1 to accumulate cyclic AMP upon subsequent challenge with PGE1 is primarily due to a selective desensitization of the PGE1-activated adenylate cyclase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Use of polarized light for quantitative determination of the adjustment of the tangential fibres in articular cartilage.

According to recent research the course of the tangential fibres is gaining increasing importance for the analysis of the first signs of pathological alterations in the articular cartilage. In a model-test, parallel-running synthetic double-refracting filaments, rotated between polarisator and analysator at right angles to each other effect an extinction curve which has two maxima at 45 degrees and the minimum at 0 degrees. Crossing filaments at different angles effects curves which are specific for the different angles in such a manner that with increasing angles to 45 degrees the curves approximate to a horizontal line. On the other hand the course of the different curves make it possible to determine corresponding angles. Then the same method is used to estimate the mean crossing-angles of tangential fibres in histological sections of articular cartilage with masked collagen fibres. The method is suitable for a quantitative calculation of the crossing-angles between 0 degrees and 45 degrees, which cannot be defined by the split-line method of Hultkrantz. In contrast to the conditions of the scanning electron microscope, the integrating nature of the polarized light is advantageous because it permits analysis of a more extensive visual field. From comparisons with the test model, a considerable variety of crossing angles of tangential fibres in the cartilage can be shown to exist.

Aged↗
PubMed1975

Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells.

The characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed.

Adenine↗
PubMed1970

Transfer of apiose from UDP-apiose to 7-O-(beta-D-glucosyl)-apigenin and 7-O-(beta-D-glucosyl)-chrysoeriol with an enzyme preparation from parsley.

An enzyme preparation from parsley (Petroselinum hortense Hoffm.) catalyses the formation of apiin (7-O-[beta-D-apio-furanosyl(1-->2)beta-D-glycosyl]-5,7,4'-trihydroxyflavone) from 7-O-(beta-D-glycosyl)-apigenin and UDP-apiose and of the corresponding chrysoeriol-7-apiosyl-glucoside from 7-O(beta-D-glucosyl)-chrysoeriol and UDP-apiose. Neither free apiose nor cyclic apiose-1,2-phosphate can function as a substrate for the transfer reaction.

Journal Article↗
PubMedDate not supplied

Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: mechanism of agonist-specific desensitization.

The mechanism underlying agonist-induced loss of responsiveness to catecholamines and prostaglandins has been investigated in human astrocytoma cells. Pulse-labeling of the cells with [3H] adenine during the time course of exposure to either norepinephrine or prostaglandin E1 (PGE1) demonstrated a reduction of the rate of incorporation of label into cyclic AMP within 5 min after exposure of the cells to either agonist. The loss of responsiveness observed by this technique was essentially agonist-specific during the first 30 min of exposure of the cells to either norepinephrine or PGE1. The rate constant for degradation of cyclic AMP throughout a 60 min exposure to either norepinephrine or PGE1 did not change suggesting that loss of responsiveness is not related to increased phosphodiesterase activity. The results are discussed in terms of a standard theoretical model for the regulation of the steady state level of an intermediate in a reaction sequence in which the rate of synthesis of the intermediate follows zero order kinetics and the rate of degradation follows first order kinetics. The hypothesis is put forth that agonist-induced desensitization is caused by an agonist-specific reduction in the rate of synthesis of cyclic AMP that follows rapidly after the initial stimulation of adenylate cyclase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗