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R Klysner

Publications and source records attributed to R Klysner.

36 records · Page 2Linked to original sources

Forskolin-stimulated adenylate cyclase activity in rat cerebral cortex following chronic treatment with psychotropic drugs.

Rats were treated with lithium, imipramine, reserpine, and lithium combined with imipramine or reserpine. Lithium was given in the diet (40 mmol/kg) resulting in a serum-Li+ level of 0.5-0.6 mmol/l. Other drugs were dissolved in 0.9% saline and given intraperitoneally once or twice daily. After 3 weeks of treatment, forskolin-stimulated adenylate cyclase activity was measured in cerebral cortex homogenates. Reserpine did not affect the forskolin stimulation, while both imipramine and lithium caused a decrease in this activity. The combined treatments lithium-imipramine and lithium-reserpine also exhibited a clear decrease in forskolin stimulation, but the effect of concomitant lithium and imipramine treatment did not differ from the effect seen after any of the treatments alone. The unstimulated activity was unaltered by all treatments. The inhibition of lithium and imipramine on the forskolin stimulation indicates an interference of these two drugs with the forskolin-mediated activation of the adenylate cyclase.

Adenylyl Cyclases↗

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↗

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↗

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↗

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↗

Increased polymorphonuclear leukocyte cGMP levels induced by the human lympholine, leukocyte migration inhibitory factor (LIF).

The possible involvement in vitro of 3', t'-cyclic GMP (cGMP) in the mechanism of action of the lymphokine, leukocyte migration inhibitory factor (LIF), was investigated. Partially purified LIF-rich supernatants, but not their control counterparts, induced a 2-fold increase in the cGMP levels of purified human polymorphonuclear (NMN) leukocytes. The effect was no influenced by heat-inactivated horse serum; it was manifested within 3 min of exposure to LIF and it subsided within 180 min. LIF and the supernatant factor responsible for the cGMP-generating effect were both rendered inactive by treatment with the serine esterase and protease inhibitor, phenylmethylsulfonyl fluoride, indicating that these factors are closely related, if not identical. A potent phosphodiesterase inhibitor, dipyridamole (2 x 10(-4) M), induced a 3- to 5-fold increase in PMN leukocyte cGMP levels, but combined treatment with purified LIF and dipyridamole did not add to this effect. This suggests that the cGMP-generating factor acts on the biochemical pathway that degrades cGMP.

Cyclic GMP↗

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↗

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↗

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↗

A simple and inexpensive protein binding assay for cyclic AMP in biological materials.

We have developed a simple and inexpensive method for largecapacity cAMP determination in biological materials. The assay is based on competitive binding of 3H-cAMP to proteins isolated from rabbit skeletal muscle. Bovine serum albumin is added to the incubate to reduce non-specific interference. Separation of free and bound radioactivity is performed by (NH4)2SO4 precipitation allowing determination of either free or bound fraction. In the latter case, all procedures are performed in the same tube, to which is finally added 1.2 ml of scintillation fluid for counting. By this only one fourth. The method has been applied to rat tissue extracts and urine with satisfactory sensitivity, precision and accuracy.

Ammonium Sulfate↗

Enhanced histamine- and beta-adrenoceptor-mediated cyclic AMP formation in leukocytes from patients with endogenous depression.

Beta-adrenoceptor-mediated cyclic AMP formation was found to be increased in leukocytes from manic-depressive patients during untreated depression when compared with euthymic patients treated with antidepressants. The difference was dependent on the stimulation used (isoprenaline or a combination of noradrenaline and phentolamine) and was only significant when the combination was used. Histamine-stimulated cyclic AMP formation in leukocytes was enhanced in patients with untreated depression, both when compared with euthymic patients suffering from manic-depressive illness, with or without treatment with antidepressant drugs, and also when compared with control persons without any known psychiatric disease. Although at variance with the results of some other studies on the same topic, the results of the present study indicate that changes in receptor function in leukocytes may be a state-dependent marker in depressive illness.

Adult↗