Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Summary Adults rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3,5-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3,5-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.Acknowledgments. This research was supported by Public Health Service Grant NS-14355.     

Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields.

Effects of N6, O2 dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective.     

Renal effects of 8-substituted derivatives of adenosine 3',5'-cyclic monophosphate in dogs

The renal effects of nine, 8-substituted derivatives of 3',5'-cyclic monophosphate were studied in anesthetized mongrel dogs. Infusion of the compounds into a renal artery resulted in an increase of renal blood flow without any effect on blood pressure. Diuretic and natriuretic effects are evident with 6 of the 9 derivatives. As these 8-substituted analogues exert renal effects in a manner similar to that seen with the parent nucleotide, cyclic adenosine 3',5'-monophosphate, they may serve as useful pharmacological agents in vivo.     

Correlation of immunogenicity with suppression of lymphocyte adenosine 3',5'-monophosphate-dependent protein kinase.

Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals. The magnitude of depression increased with the immunogenicity of the tumor. The depressed enzyme activity was the result of a reduced Vmax for adenosine 3',5'-monophosphate (cAMP)-stimulated histone phosphorylation.     

Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture.

2O, 6N-butyryl, 3', 5'-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP greater than 6N-bu cAMP greater than 2O-bu cAMP = AMP greater than butyrate. The inhibition caused by the first three chemicals is greater than 70%.     

Effect of pyrophosphate and orotidine monophosphate on cytosine deaminase regulatory properties

The maximal velocity of the reaction (Vmax) and the half-saturation constant (K0.5) values of the S. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.     

Correlation between 3',5', c-AMP levels and thyrotropin in separated rat pituitary thyrotropic cells.

The correlation between 3',5', c-AMP levels, TSH content and secretion of separated thyrotropic cells was studied. Incubation of the separated cells with 1, 10 and 100 ng of TRH does not change the 3',5',c-AMP levels, despite the significant rises of the TSH level. Dibutyryl c-AMP causes rise in TSH content, with no indication of its secretion. PGE2 10(-5) increased 3'5',c-AMP levels with no change in the content or secretion of TSH in separated thyrotropic cells.     

Effects of isoproterenol and dopamine on the myocardial hexose monophosphate shunt.

Long-term exposure of rats to isoproterenol and dopamine resulted in an increase of glucose-6-phosphate dehydrogenase activity and a greater availability of 5-phosphoribosyl-l-pyrophosphate in the myocardium. These results are interpreted to indicate an enhanced flow through the hexose monophosphate shunt.     

Cyclic AMP accumulation in human fibroblast cultures: diabetics compared with normals

Isoproterenol-stimulated accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in skin fibroblast cultures from type 2 diabetics was twice as high as in fibroblasts from control subjects.     

Effects of isoproterenol and dopamine on the myocardial hexose monophosphate shunt

Summary Long-term exposure of rats to isoproterenol and dopamine resulted in an increase of glucose-6-phosphate dehydrogenase activity and a greater availability of 5-phosphoribosyl-1-pyrophosphate in the myocardium. These results are interpreted to indicate an enhanced flow through the hexose monophosphate shunt.Supported by the Deutsche Forschungsgemeinschaft (Zi 199/1). The excellent technical assistance of Miss G. Steinkopff is gratefully acknowledged.     

Capillary blood flow in the testes and testosterone secretion in the starved rat

Summary The average capillary blood flow in the testes was found to be 181 l/min/g testis tissue (n=19) in rats starved for 5 days and 273 l/min/g (n=18, p<0.01) in the control group. Plasma testosterone was significantly decreased in the starved animals (1.00±0.06 ng/ml vs 5.43±0.63 ng/ml). When starved and control rats were stimulated with human chorion gonadotropin, testosterone values in plasma were greatly increased in both groups. The capillary blood flow was not altered. The data indicate that human chorion gonadotropin can stimulate testosterone production in the starved rat without influencing the reduced capillary blood flow.     

The effects of continuous chloroform and halothane anesthesia on plasma prolactin levels in ovariectomized estrogen-treated rats

Summary In ovariectomized, estrogen-treated rats bearing indwelling aortic catheters, continuous inhalation of chloroform or halothane resulted in increases in plasma prolactin levels 10 min after the exposure to the anesthetics. The plasma prolactin levels over the subsequent 2 h, however, were not significantly different from that of the control animals.Supported by NSF Research Grant BMS 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding assistance in the performance of the prolactin RIA and the art work.     

Effect of pyrophosphate and orotidine monophosphate on cytosine deaminase regulatory properties

Summary The maximal velocity of the reaction (V_max) and the half-saturation constant (K_0.5) values of theS. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.     

The deiodinase family: selenoenzymes regulating thyroid hormone availability and action

Thyroid hormones control growth, development, differentiation and metabolism in vertebrates. Most of the actions of the active thyroid hormone T3 (3,5,3'-triiodo-L-thyronine) are exerted via ligand-activated nuclear T3 receptors. Activation of the secretory product of the thyroid gland, L-thyroxine (3,3',5,5'-tetraiodo-L-thyronine), or T4, is catalyzed by two enzymes, iodothyronine-5'-deiodinases type I and type II. Inactivation of T4 and T3 occurs via type III iodothyronine-5-deiodinase and to some extent by type I 5'deiodinase. Complementary DNAs (cDNAs) encoding the substrate-binding selenocysteine-containing subunits of the deiodinases were cloned, though some controversy still exists on the type II 5'-deiodinase subunits. Characterization of tissue-specific expression patterns indicates that these selenium-dependent enzymes exert tight control on local and systemic availability of active T3. Thus, deiodinases are envisaged as guardians to the gate of thyroid hormone action mediated by T3 receptors.     

Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane

In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end-tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant.     

Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol, caffeine, or phenobarbital administration.

Decreased activities of both the inhibitory modulator of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependent of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.     

Time course study of the changes in blood glutathione induced by acute ethanol intoxication in the rat

Acute ethanol treatment of rats (5 g/kg) has a biphasic effect on the glutathione content of the erythrocyte. After 3 h of intoxication there is a diminution in total GSH equivalents, followed by a recovery to basal values 6 h after treatment. The decrease of total GSH equivalents is mainly due to a diminution of the oxidized form of the tripeptide. Concomitantly a marked increase in the plasma level of glutathione was found at 3 h, followed by a diminution to values obtained at time zero.     

Nitroglycerin-induced desensitization of vascular smooth muscle may be mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis

The purpose of this study was to investigate the hypothesis that nitroglycerin-induced desensitization of vascular smooth muscle is mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis. Norepinephrine-induced contraction and increased levels of inositol monophosphate, a measure of phosphatidylinositol hydrolysis, in rat aorta. Prior treatment with nitroglycerin inhibited both the norepinephrine-induced contraction and the elevated levels of inositol monophosphate to the same relative magnitude. The nitroglycerin-induced inhibition of contraction and inositol monophosphate formation were prevented in tissues desensitized with nitroglycerin. These results suggest that: nitroglycerin may inhibit vascular smooth muscle contraction through cyclic GMP-inhibition of phosphatidylinositol hydrolysis and desensitization to the relaxant effects of nitroglycerin may be due to disinhibition of the hydrolysis.     

Induction of the in vitro p-hydroxylation of14C-amphetamine stereoisomers in phenobarbital-treated rats

Summary The rate of p-hydroxylation of¹⁴C-(-)-amphetamine by liver microsomes was higher than that of (+)-isomer in phenobarbital-treated male rats. The apparent K_m values for (-)- and (+)-amphetamine hydroxylation were 4.54×10^–5 M and 2.27×10^–5 M respectively, in both treated and control animals.