Cyclic adenosine-3',5'-monophosphate content in the limbic system structures of the rat brain on the administration of corticosteroids

The effect of hydrocortisone and DOCA on the cAMP content in the hypothalamus, hippocampus and striate body of the rat brain was investigated. Single (determined after 1 and 24 hours) and repeated (7 days) hydrocortison administration in a dose of 5 mg/100 g body weight was accompanied by an increase in the cAMP concentration in the brain structures under study. Single administration of DOCA in a dose of 0.5 mg/100 g body weight did not produce any changes in the cAMP level in the structures of the rat brain limbic system; however, the dose of 2.5 mg raised the cAMP level. Prolonged administration of the hormone in the above doses dod not change the cAMP level in the brain structures. Only the hippocampus showed a 210% increase in the cAMP level during DOCA administration in a dose of 0.5 mg.     

Formation of cyclic adenosine-3',5'-monophosphate in phagocytosis]

The content of cAMP in the phagocytizing macrophages increased, especially in the phagocytosis of live microbes. cAMP formed in phagocytosis was determined in the incubation medium, whereas in the cells its content remained practically unchanged. In the administration of E. coli 055 to the germ-free guinea pigs the concentration of cAMP was found to be increased in the mucosa cells of the small intestine and in the blood serum; this fact indicated that adenylcyclase system participated in the reactions of the interrelations of the microorganisms with the epithelial cells of the smal intestiine.     

Cyclic adenosine-3',5'-monophosphate level in donor plasma]

The method of competitive protein binding was applied to the study of content of cyclic adenosine-3',5'-monophosphate (cAMP) in donor plasma one day before and immediately after the donation of 200 ml of blood. The work was performed by Gilman's radiochemical method. Two types of reaction of donors to donorship were revealed: without any changes and with the changes of the cAMP level. In accordance with these reactions the donors were divided into two subgroups--the stable and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and the reactive ones. In repeated donors the cAMP level was higher than in the primary ones, and at the time of blood recovery it increased even more particularly among persons of "reactive" type. In primary donors of reactive type the cAMP content before the blood donation was either below or over the mean value and either increased or decreased to the mean level after the blood loss.     

Regulatory role of DOPA and components of the cyclic adenosine-3',5'-monophosphate system]

It was shown on albino mice that when DOPA-3H (20 muCi/mouse) was administered before nonradioactive DOPA (1 mg/mouse) tritium accumulation in the tissue of Harding-Passi's melanoma of these mice proved to increase. Melanoma radioactivity in this experimental group was double that in the tumour tissue of the animals to which DOPA-3H alone was administered. Examination of the adenylate cyclase, phosphodiesterase activity and of the level of cAMP in melanoma of mice 2 hours after DOPA administration (1 mg/mouse) showed accumulation of cAMP and an increase in the phosphodiesterase activity; as to adenylate cyclase activity--it fell. It is suggested that DOPA realizes its effect not only as melanin precursor, but also through the cAMP system, influencing the melanogenesis enzymes activity.     

Cyclic adenosine-3',5'-monophosphate and folate transport in rat jejunum

The intestinal transport of 5-methyltetrahydrofolate and pteroylmonoglutamate was examined in everted sacs of rat jejunum exposed to compounds which increase intracellular cyclic adenosine-3', 5'-monophosphate. Adenyl cyclase stimulators (hydrocortisone and prostaglandin), phosphodiesterase inhibitors (3-isobutyl-l-methylxanthine, aminophylline and papaverine), and dibutyryl adenosine-3',5'-cyclicmonophosphate added to the mucosal medium inhibit the mucosal-to-serosal transport of physiological concentrations of 5-methyltetrahydrofalate and pteroylmonoglutamate. Transport inhibition is correlated with the ability of these agents to increase cellular cyclic adenosine-3', 5'-monophosphate. The active, carrier-mediated transport system of folate compounds is highly sensitive to the increase in cyclic adenosine-3', 5'-monophosphate level, while the diffusion system is insensitive. These data indicate that the active transport system of folates is modulated by cellular cyclic adenosine-3', 5'-monophosphate.     

Inhibition of rat heart and brain cyclic adenosine-3',5'-monophosphate phosphodiesterase in vitro under the influence of neurohormone C]

The work was devoted to one of the new neurohormones (neurohormone "C") obtained from the bovine hypothalamus which produced a pronounced relaxation of the coronary vessels. A study of the effect of "C" on cyclic 3',5'-adenosine monophosphate (cAMP) phosphodiesterase (PDE) showed "C" to be a potent inhibitor of PDE in the crude PDE-preparations of the rat heart and brain. Experiments were carried out on the 2000 g supernatant obtained from the homogenized tissues. It is supposed that the relaxant effect of "C" on the coronary vessels is due to its inhibitory action on PDE mediated by the accumulated cAMP.     

Differential effects of cyclic adenosine-3',5'-monophosphate on phosphorylation of rat liver nuclear acidic proteins

The effects of cyclic AMP on the phosphorylation of different acidic proteins of rat liver nuclei were examined in vivo and in vitro. N⁶,O²′-dibutyryl cyclic AMP selectively stimulated in vivo phosphorylation of specific nuclear proteins more than twofold within 15 min after injection. Cyclic AMP caused only a small stimulation of phosphorylation of acidic proteins in isolated nuclei but the stimulation was selective for specific proteins. When isolated nuclear acidic proteins were incubated with a soluble cyclic AMP-dependent protein kinase, the cyclic nucleotide stimulated total phosphorylation about 1.7-fold. These results support the view that the regulatory effects of cyclic AMP may involve phosphorylation of acidic proteins associated with DNA in the chromatin.     

Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats]

The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues.     

Effect of L-DOPA on cyclic adenosine-3',5'-monophosphate in neurogenically damaged cardiac muscle

During electric stimulation of the aortal reflexogenic zone in rabbits, administration of L-DOPA prevented the reduction of the level of cyclic adenosine-3',5'-monophosphate (cAMP) in the cardiac muscle and blood plasma. This is likely to be related to L-DOPA ability to participate in the biosynthesis of endogenous catecholamines, and thus to stimulate the synthesis of cAMP.     

Organ and tissue cyclic adenosine-3', 5'-monophosphate during the process of the body's adaptation to extreme factors]

Various by nature extreme factors (hypoxic hypoxia, CO intoxication, chemical influence, noise and hypokinesia) caused similar changes in cAMP levels in different organs of albino rats (liver, the great cerebral hemispheres, heart). There was a significant increase in cAMP concentrations during the first stages of the influence and a progressive fall when the influence was continued. This fall was particularly expressed when the extreme factors used were of marked intensity. The authors consider the universality of the ascertained regularity to be a reflection of one of the central adaptive mechanisms of cell and the organism as a whole.     

Lack of adenosine-3',5'-monophosphate receptor protein and apparent lack of expression of adenosine-3',5'-monophosphate functions in Mycobacterium smegmatis CDC 46

The presence of adenosine-3',5'-monophosphate (cAMP), adenylate cyclase and the effect of glucose on cAMP levels in Mycobacterium spp have been reported earlier. To understand the role(s) of cAMP in these organisms, the induction of various enzyme systems was studied. Beta-galactosidase and L-tryptophanase were present at low levels of activity and could not be induced. Glycerokinase was inducible but the induction was not affected by glucose. The fructose uptake system was inducible, and the induction was lowered in the presence of glucose, but cAMP could not reverse the inhibition. cAMP binding protein was not detectable under a variety of conditions. On the basis of the lack of active cAMP binding protein, a model has been proposed to explain the apparent lack of expression of cAMP function in Mycobacterium smegmatis CDC 46.     

Cyclic adenosine-3',5'-monophosphate content of the brain in conditions of extreme stimulation]

The content of brain cAMP was investigated under conditions of electric stimulation of immobilized rats which resulted in the development of reflex dystrophies of the internal organs. There was found a pronounced decrease in the amount of cAMP in the rat brain which developed 15 minutes after the beginning of extreme stimulation and remaained at the same low level for 3 hours after the electrical irritation. Reduction of the cAMP level was probably connected with noradrenaline and other biologically-active amine deficiency in the brain under conditions of extreme stimulation.     

Plasma cyclic adenosine-3', 5'-monophosphate response to glucagon in patients with liver disease.

The change in plasma cyclic adenosine-3'', 5''-monophosphate (AMP) was measured after intravenous injection of 1 mg of glucagon in 10 normal subjects and 30 patients with various forms of liver disease. Patients with cirrhosis and those with intrahepatic cholestasis responded normally but in patients with extrahepatic obstruction the plasma cyclic AMP response was considerably increased. Six of the eight patients with cirrhosis and a surgically created portacaval shunt had very reduced responses. This test may prove to be diagnostically important, particularly in differentiating surgical from non-surgical jaundice.     

An equilibrium study of the cooperative binding of adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate to the adenosine cyclic 3',5'-monophosphate receptor protein from Escherichia coli

The binding of adenosine cyclic 3',5'-monophosphate (cAMP) and guanosine cyclic 3',5'-monophosphate (cGMP) to the adenosine cyclic 3',5'-monophosphate receptor protein (CRP) from Escherichia coli was investigated by equilibrium dialysis at pH 8.0 and 20 degrees C at different ionic strengths (0.05--0.60 M). Both cAMP and cGMP bind to CRP with a negative cooperativity that is progressively changed to positive as the ionic strength is increased. The binding data were analyzed with an interactive model for two identical sites and site/site interactions with the interaction free energy--RT ln alpha, and the intrinsic binding constant K and cooperativity parameter alpha were computed. Double-label experiments showed that cGMP is strictly competitive with cAMP, and its binding parameters K and alpha are not very different from that for cAMP. Since two binding sites exist for each of the cyclic nucleotides in dimeric CRP and no change in the quaternary structure of the protein is observed on binding the ligands, it is proposed that the cooperativity originates in ligand/ligand interactions. When bound to double-stranded deoxyribonucleic acid (dsDNA), CRP binds cAMP more efficiently, and the cooperativity is positive even in conditions of low ionic strength where it is negative for the free protein. By contrast, cGMP binding properties remained unperturbed in dsDNA-bound CRP. Neither the intrinsic binding constant K nor the cooperativity parameter alpha was found to be very sensitive to changes of pH between 6.0 and 8.0 at 0.2 M ionic strength and 20 degrees C. For these conditions, the intrinsic free energy and entropy of binding of cAMP are delta H degree = -1.7 kcal . mol-1 and delta S degree = 15.6 eu, respectively.     

Effect of cyclic adenosine-3', 5'-monophosphate on cells of experimental lympholeukemia L-5178]

A study was made of the effect of cyclic adenosine-3',5'-monophosphate (cAMP) dibutyril-cAMP and theophylline (phosphoesterase inhibitor - an enzyme transforming adenosine-3'-5'-monophosphate into adenosine-5'-monophosphate) on the intensity of proliferation (by the increase in the content of nucleic acids in the culture), DNA synthesis (by the H3-thymidine incorporation) and on the transplantation properties (the capacity to repopulation in the animal organism) of leukemic cells of the L-5178 strain. It was found that cAMP in a concentration of 0.8 mM considerably inhibited the H3-thymidine incorporation, retarded the proliferation and decreased the transplantation capacity of leukemic cells. Theophylline and dibutyril-cAMP had a comparatively low inhibitory capacity on the DNA synthesis, proliferative activity and the transplantation properties of the cells.