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Biomedical subjects

A Geisler

Publications and source records attributed to A Geisler.

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

Characterization of and drug influence on a calmodulinsensitive phosphodiesterase purified from bovine brain.

A calmodulin-sensitive phosphodiesterase was purified from bovine brain. The purification procedure involved ammonium sulphate fractionation, two chromatographic steps on DEAE-cellulose, gel-filtration on Sephadex G-200, and finally one DEAE-cellulose run, and gave a 2300-fold purification. The purified phosphodiesterase had a Vmax for cyclic AMP of 126 mumol/mg protein X min. and was activated 8-fold by addition of calmodulin and calcium. According to SDS-electrophoresis the purified enzyme contained one major peptide of 59,000 daltons, but the preparation was not homogeneous. The enzyme was characterized kinetically and with regard to the effect of cations, pH temperature, and nucleotides. Furthermore, the influence in vitro on enzyme activity of several classes of drugs, e.g. antidepressants, neuroleptics, antiallergics, platelet inhibitors, and some "reference phosphodiesterase inhibitors" was investigated.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1983

Cyclic AMP phosphodiesterase activity in rat brain following chronic treatment with lithium, imipramine, reserpine, and combinations of lithium with imipramine or reserpine.

The adaptability of the cyclic AMP phosphodiesterase (PDE) following chronic treatment (4-6 weeks) with lithium, reserpine, imipramine, and combinations of lithium with imipramine or reserpine has been studied in rat brain tissue. All drugs, except lithium, were given intraperitoneally once a day. Control animals received only vehicle. Lithium was given in the diet in a concentration yielding a plasma level of 0.5-0.6 mmol/l. The PDE activity was measured in homogenates from cerebral cortex and "limbic" forebrain. These two brain areas were both found to contain three types of PDE activity. One was mainly associated with the pellet after a 10,000 X g centrifugation for 10 min. This enzyme hydrolyzed both cyclic AMP and cyclic GMP with a Km value of 130 +/- 48 microM for cyclic AMP, but was insensitive to calcium and calmodulin. Two types were mainly found in the supernatant after the centrifugation with Km values cyclic AMP of 300 +/- 108 microM and 4 +/- 3 microM, respectively. The former hydrolyzed both cyclic AMP and cyclic GMP and was stimulated 7-fold by calcium and calmodulin, while the latter only hydrolyzed cyclic AMP and was insensitive to calcium and calmodulin. None of the treatments affected the "pellet" enzyme or the low affinity enzyme from the supernatant. However, lithium treatment, even combined with reserpine or imipramine, increased the high affinity enzyme. This increase was also apparent in the DEAE-ion exchange chromatographic profile of the PDE enzymes.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Possible regulatory role of histamine in human platelet function examined by thrombin-induced serotonin release.

The influence of histamine on human platelet function was studied by thrombin-induced serotonin release. The thrombin-induced 3H-serotonin release was confirmed to be a rapid process which does not require external calcium. Histamine was found to reduce the release of serotonin and the inhibition was abolished when H1-plus H2-antagonists were added together with histamine. H1- and H2-receptor stimulation was examined in two ways, by a combination of histamine with cimetidine or diphenhydramine and by the selective agonists 2-(2-pyridyl)-ethylamine and impromidine. In both instances H1- and H2-stimulation was found to reduce the platelet serotonin release. These results suggest a regulatory role of histamine in the platelet function by stimulation of platelet H1- and H2-receptors.

Blood Platelets↗
PubMed1981

Possible role of histamine in rheumatoid arthritis. Treatment with cimetidine and mepyramine.

Basophilocytes from patients with rheumatoid arthritis (RA) responded to leukocyte nuclei from normal persons with histamine release; a similar histamine release induced by the nuclear components RNA and DNA has been demonstrated previously. A role of histamine in RA is also supported by the findings of clinical improvement during treatment with H1 and H2 antihistamines in six of 12 patients with RA in active phase, whereas four showed definite deterioration.

Adolescent↗
PubMed1981

On the mechanism of inhibition of rat fat cell adenylate cyclase by lithium.

This study aimed to elucidate the mechanism by which Li+ inhibits adenylate cyclase (AC) in vitro. It was found that Li+ inhibited the norepinephrine-(NE) and the fluoride-(F-) stimulated AC activities of rat fat cell ghosts of Li+ concentrations above 10 mM. The basal enzyme activity was unaffected even at 80 mM of Li+. Li+ inhibited the NE-induced AC activity in a mainly non-competitive way, but the inhibitory effect decreased with increasing concentrations of NE. The inhibition by Li+ of both NE- and F- -stimulated AC activities was antagonized by Mg2+. The Mg2+ antagonism of the Li+-induced inhibition of the NE-stimulated AC activity was independent of the NE concentration. Furthermore, Ca2+, inhibiting AC activity by a Mg2+ antagonism, abolished the inhibitory effect of Li+. It is suggested that Li+ affects both the Ka of NE and the Vmax of AC through 1) an inhibitory action of LiATP3- at the catalytic site of AC or 2) an inhibitory action of Li+ at an allosteric Mg2+ site of AC.

Adenosine Triphosphate↗
PubMed1980

An investigation into the fine structure of the ligated rat ureter.

The normal structure of the ureter of the rat is described and compared with the results of earlier work. Research on arteries left in situ stimulated morphological investigation of the ligated ureter proximally and distally to the ligature. As in ligated blood vessels, an increase in modified muscle cells with accompanying increase in connective tissue (particularly proximally to the ligature) occurs in the ureter. In association with quantitative changes, qualitative changes in the formation of collagen and in the arrangement of fibrils were found, although not so marked as in arteries subjected to "load failure". During a comparison of the ureteric walls on either side of a ligature intracellular collagen was found. The results of earlier work on ligated ureters are discussed, together with the present findings. The reactions of ureteric and arterial walls subjected to similar "load failures" are compared. Qualitative changes in the intercellular substance are considered in connection with the findings in cases of pathological processes in the walls of blood vessels. Several possibilities are suggested with regard to the interpretation of the intracellular collagen.

Animals↗
PubMed1980

Histamine H2 receptor-mediated cyclic AMP formation in human platelets.

The influence of histamine on the level of cyclic AMP was studied in human platelets. A dose-related accumulation of cyclic AMP was obtained, culminating at about 10 microM of histamine. The response was blocked by the H2 antagonist cimetidine, but neither by H1 antagonists nor by alpha- or beta-adrenergic antagonists. The results suggest that histamine causes an accumulation of cyclic AMP in human platelets by stimulation of H2 receptors. Cyclic AMP accumulation is supposed to be associated with a depression of the platelet function, and a reduced platelet release reaction was actually demonstrated by our results.

Blood Platelets↗
PubMed1980

Dissociation by lithium of hormone-induced formation of cyclic AMP and release of glycerol in isolated rat fat cells.

It has been suggested that lithium exerts some of its pharmacological actions by inhibition of the membrane-bound enzyme adenylate cyclase. However, the relationship between the lithium inhibition of adenylate cyclase and the corresponding physiological parameters, e.g. lipolysis, has not been investigated. In the present study it was found that lithium inhibited both the norepinephrine-induced accumulation of cAMP and release of glycerol in isolated rat fat cells, but only in the lower dose range of norepinephrine. At maximally effective concentrations of norepinephrine, where in the presence of 40 mM of lithium the formation of cAMP was reduced by approximally 40%, lipolysis remained unaffected. The basal content of cAMP and the basal release of glycerol were not inhibited by lithium. In addition to the inhibitory effect of lithium, lithium was found to stimulate the release of glycerol. This stimulatory effect of lithium may be explained by a prevention by lithium of the feedback inhibition by free fatty acids of adenylate cyclase and/or triglyceride lipase, since it could be avoided by increasing the concentration of bovine serum albumin in the incubation medium. It is concluded that lithium by inhibition of hormone-stimulated adenylate cyclase activity inhibits lipolysis only at submaximal hormone concentrations. This dissociation by lithium of cAMP accumulation and glycerol release may suggest that at least at high concentrations of norepinephrine cAMP-independent factors are involved in lipolysis.

Adipose Tissue↗
PubMed1979

Influence of lithium on cyclic AMP accumulation in isolated rat fat cells.

Lithium inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclase in vitro. It was found that lithium inhibited both the norepinephrine- and the glucagon-induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. It is suggested that lithium affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action.

Adenylyl Cyclase Inhibitors↗
PubMed1977

Allergic reactions, cyclic AMP and histamine release.

Both isobutylmethylxanthine and theophylline increased the level cyclic AMP in the mast cell. Theophylline reduced the allergic histamine release, whereas isobutylmethylxynthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is too simple.

Animals↗
PubMed1977

Cyclic AMP and allergic histamine release. Influence of methylxanthines on rat mast cells.

Both isobutylmethylxanthine and theophylline increased the level of cyclic AMP in rat mast cells. Theophylline reduced the allergic histamine release, whereas isobutylmethylxanthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is inadequate.

Animals↗
PubMed1977

Adenylate cyclase activity in corpus striatum of rats with porto-caval anastomosis.

Altered catecholamine receptor sites within the striatum have been proposed to be an important pathogenetic factor in hepatic and porto-systemic encephalopathy and coma. The unstimulated, fluoride-, norepinephrine- and dopamine-stimulated adenylate cyclase activity were measured in the corpus striatum of rats with a four weeks old end-to-side porto-caval anastomosis. There was no difference in unstimulated, fluoride- or hormone-stimulated adenylate cyclase activity between porto-caval shunted and sham-operated rats. The in vitro dose-response curves of norepinephrine and dopamine were similar in both groups of animals. Half-maximum and maximum stimulation were achieved in shunted and sham-operated rats by identical concentrations of norepinephrine and dopamine, respectively. The results indicate that neither changes in unstimulated adenylate cyclase activity nor changes in the response of adenylate cyclase activity to fluoride, norepinephrine and dopamine had developed in the rats at the stage studied.

Adenylyl Cyclases↗