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Biomedical subjects

J Christophe

Publications and source records attributed to J Christophe.

At least 217 records · Page 12Linked to original sources
PubMed1981

Similar characteristics of guanine nucleotide regulatory sites involved in adenylate cyclase activation, specific GTPase activity, and cholecystokinin binding in rat pancreatic plasma membranes.

The specificity of guanine nucleotide regulatory site(s) of rat pancreatic plasma membranes involved in adenylate cyclase activation, basal and cholecystokinin (CCK)-stimulated specific GTPase activity, and [125I]-CCK-33 binding was documented. The Km (for GTP) and Ki (for other nucleotides) of basal and CCK-8-dependent GTPase showed similar specificity, decreasing in the order GTP gamma S approximately GTP approximately Gpp[NH]p greater than ITP greater than GDP beta S greater than UTP, suggesting the identity of basal and CCK-stimulated GTPase activities. The same potency order for these nucleotides was obtained when tested as activator (Ka) or inhibitor (Ki for GDP beta S) of adenylate cyclase, in the presence of CCK-8. The IC 50 of these nucleotides on the binding of [125I]-CCK-33 indicated a similar specificity for nucleotide binding sites interacting with CCK receptors (GTP gamma S approximately Gpp[NH]p approximately GTP greater than ITP approximately GDP beta S greater than UTP). In membranes preactivated with 0.3 micron CCK-8 and 30 micron Gpp[NH]p or GTP gamma S, then washed free of hormone and unbound nucleotide, persistent effects of the nonhydrolyzable nucleotides were observed on the three activities tested. The present data indicate that the guanine nucleotide regulatory units involved in adenylate cyclase activation, GTPase activity and CCK binding have similar properties in rat pancreatic plasma membranes.

Adenylyl Cyclases↗
PubMed1981

Effects of portacaval shunt on the genetically obese Zucker Rat.

Male adult obese (fa/fa) Zucker rats with high hypertriglyceridemia and hyperinsulinemia, and mild hypercholesterolemia were submitted to a portacaval shunt in order to examine the effects of this shunt on blood lipids and lipid synthesis. Sham-operated pair-fed obese (fa/fa) Zucker rats, obese (fa/fa) Zucker rats fed ad libitum, and lean (Fa/?) littermates fed ad libitum served as controls. In fa/fa rats 3 wk after portacaval shunt, fasting serum values of triacylglycerol (-70%) and cholesterol (-43%) were lower and plasma total glucagon was higher (+68%) than in pair-fed sham-operated fa/fa controls. In the same rats 4 wk after portacaval shunt and while fed ad libitum, serum protein was reduced by 22%, plasma pancreatic glucagon was 100% higher, and the hyperinsulinema was not modified. At that time, the wet weight of the liver and its total content in DNA, RNA, protein, and glycogen was decreased by 43%, 22%, 34%, 39%, and 60%, respectively. The in vivo incorporation of 3H2O into liver fatty acids was 76% lower and that into liver cholesterol eas 43% lower, per total organ, while the labeling of glyceride fatty acids was not modified in epididymal adipose tissue when compared with pair-fed fa/fa Zucker rats. In conclusion, portacaval shunting lowered blood triacylglycerol and cholesterol levels in fa/fa rats, and this was due, at least partially, to reduction in hepatic lipogenesis and cholesterologenesis.

Animals↗
PubMed1981

Guanine nucleotide binding sites, responsible for adenylate cyclase activation and carbamylcholine binding inhibition, show similar properties in rat heart membranes.

1/ In rat heart membranes, muscarinic receptors were shown to interact with guanine nucleotide binding sites closely related, if not identical, to those activating adenylate cyclase. The dose-effect curves of GTP, p[NH]ppG, and GTP gamma S for inhibition of carbamylcholine binding (measured by competition with [3H]QNB) and for adenylate cyclase activation (measured in the presence of isoproterenol) were parallel, at both 25 degrees C and 37 degrees C. 2/ Persistent activation of adenylate cyclase was obtained in heart membranes preincubated with p[NH]ppG or GTP gamma S then washed. The affinity for carbamylcholine was reduced after this pretreatment. The SO.5 of p[NH]ppG and GTP gamma S provoking persistent activation of adenylate cyclase and persistent inhibition of carbamylcholine binding were identical. Persistent inhibition of carbamylcholine binding was not additive with the inhibition observed when fresh nucleotide was added after washing. With p[NH]ppG, SO.5 values were unaffected by washing. With GTP gamma S, the SO.5 value for persistent activation of adenylate cyclase (i.e. after washing) and 330 times higher than that implementing activation (i.e. before washing). A similar change was observed when testing the SO.5 of GTP gamma S inhibition of carbamylcholine binding. This might reflect a partial release of GTP gamma S (but not of p[NH]ppG) from "spare" nucleotide binding sites during the washing period. 3/ Adenylate cyclase activity after maximal persistent activation was not increased when 0.1 mM guanine nucleotide, with or without 10 muM isoproterenol, was added to the incubation medium. In contrast, carbamylcholine binding was further decreased when fresh guanine nucleotide was added to the binding assay. This suggests that the proportion of "spare" nucleotide binding sites capable of activating the adenylate cyclase was higher than that capable to inhibit carbamylcholine binding, or that a second class of nucleotide binding sites (binding p[NH]ppG and GTP gamma S reversibly) was also able to inhibit carbamylcholine binding.

Adenylyl Cyclases↗
PubMed1980

In vitro effects of ethanol and ethanol metabolism in the rat pancreas.

1. Ethanol provoked no effect on basal and carbamylcholine-stimulated secretion of amylase from rat pancreatic fragments incubated for 1 h. 2. Ethanol enhanced in vitro synthesis of fatty acids from [1-14C]acetate and from 3H2O by 110 and 166%, respectively. The spectrum of fatty acids labelled with [1-14C]acetate in the presence of ethanol pointed to a stimulation of the malonic acid pathway, whereas the elongation of polyenoic fatty acids was unaltered. The in vitro metabolism of [1-14C]ethanol indicates that ethanol itself contributed carbon atoms to lipogenesis dose-dependently. 3. The conversion of [U-14C]glucose into sn-glycero 3-phosphate and the esterification of fatty acids into phosphatidic acids and triacylglycerols was stimulated whereas net lipolysis was unaffected. The oxidation of [U-14C]-glucose and of [1-14C]acetate to 14CO2 and the beta-oxidation of [1-14C]palmitate was reduced by 24--26%. 4. Maximal effects were produced by a 100--200 mM ethanol concentration and the concentration of ethanol evoking a similar half-maximal alteration of most processes was 20--30 mM. A 10--20 min lag period was required for the full development of these effects. 5. It is concluded that ethanol at low concentration alters the redox state of pancreatic fragments therefore favoring de novo lipogenesis and triacylglycerol formation and depressing glucose uptake and fatty acid oxidation.

Acetates↗
PubMed1980

Secretin and VIP-stimulated adenylate cyclase from rat heart. I. General properties and structural requirements for enzyme activation.

Membrane adenylate cyclase from rat heart was activated by the two gut peptides secretin and vasoactive intestinal peptide (VIP), glucagon, and the beta-adrenergic drug isoproterenol, in the presence of guanosine 5'-triphosphate (GTP). With all the stimuli tested, the optimal magnesium concentration was 5 mM, i.e. in excess over the 0.5 mM ATP substrate concentration and 0.01 mM GTP used as cofactor. Under these conditions, half-maximal adenylate cyclase activation with glucagon, secretin, and VIP was achieved at concentrations of 0.5, 0.5 and 1.0 microM, respectively. Data obtained with the secretin (7--27) fragment, a secretin antagonist, indicate that secretin and VIP acted on the same binding sites, which differed from glucagon binding sites. Structural requirements for secretin activation of cardiac adenylate cyclase were evaluated by comparing the potency and efficacy of parent peptides and synthetic analogs. The gastric inhibitory peptide GIP was inactive. When using 13 mono-or bi-substituted analogs, it appeared that amino acids in positions 1, 2, 3, 4 and 6 were of major importance while those in position 5 and 11 played a relatively minor role.

Adenosine Triphosphate↗
PubMed1980

Secretin and VIP-stimulated adenylate cyclase from rat heart. II. Impairment in spontaneous hypertension.

Cardiac adenylate cyclase activity was normal in 3 weeks-old spontaneously hypertensive rats of the Wistar-Okamoto substrain. The hormone-sensitive adenylate cyclase activity was reduced in 10 weeks-old or older animals, and secretin- and VIP-activations were definitely more impaired (by 64% and 69%, respectively) than isoproterenol- and glucagon-activations (17% and 22%, respectively). By contrast, the fluoride- and p[NH]ppG-stimulations of the enzyme were unaffected. These alterations in the adenylate cyclase system coupled to secretin and VIP appeared specific to the heart as the isolated pancreatic acinar cells from spontaneously hypertensive animals responded normally to secretin, as a liver particulate fraction responded normally to secretin and VIP, and both brain synaptic membranes and a particulate fraction of anterior pituitary to VIP.

Adenylyl Cyclases↗
PubMed1980

The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets.

Exogenous L-glutamine is actively metabolized in rat pancreatic islets. The rate of L-glutamine deamidation largely exceeds the rate of glutamate conversion to gamma-aminobutyrate and alpha-ketoglutarate. The latter conversion occurs in part by oxidative deamination, and in part by transamination reactions coupled with the conversion of 2-keto acids (pyruvate, oxaloacetate), themselves derived from the metabolism of glutamine, to their corresponding amino acids (alanine, aspartate). An important fraction of malate formed from alpha-ketoglutarate leaves the Krebs cycle and is converted to pyruvate, the process being apparently associated with the induction of a more reduced state in cytosolic redox couples. L-Glutamine abolishes the oxidation of endogenous nutrients is documented by the fact that the glutamine-induced increase in O2 consumption is much lower than expected from the rate of 14CO2 output from islets exposed to L-[U-14C]glutamine, L-Glutamine, although decreasing K+ conductance, fails to stimulate insulin release both in the absence and presence of D-glucose. It is proposed that L-glutamine represents a major fuel for pancreatic islets under physiological conditions.

Animals↗
PubMed1980

The activation of brain adenylate cyclase and brain cyclic-nucleotide phosphodiesterase by seven calmodulin derivatives.

1. A comparison has been made of the ability of seven calmodulin derivatives to displace 125I-labeled calmodulin and to activate adenylate cyclase in a brain particulate fraction. The activation of brain-soluble cyclic-nucleotide phosphodiesterase by the same calmodulin derivatives was examined in parallel. 2. In general, the dose for half-maximal inhibition of 125I-labeled calmodulin binding and the apparent Km of adenylate cyclase activation were comparable in brain membranes. These concentrations were 20--40-times higher than the corresponding apparent Km values of activation of cyclic-nucleotide phosphodiesterase. 3. Modifying the single histidine residue or both tyrosine residues exerted no influence on the biological properties of calmodulin. The carboxymethylation of two methionine residues or the amidation of several carboxyl groups reduced the activation properties of calmodulin on adenylate cyclase and cyclic-nucleotide phosphodiesterase. Altering seven lysine or four arginine residues resulted in two proteins whose activation properties on adenylate cyclase and phosphodiesterase had been modified in a way suggesting that lysine and arginine residues play distinct roles in the interaction of native calmodulin with each enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Phosphatidylinositol turnover and calcium movement in the rat pancreas.

Carbamylcholine, bombesin, pancreozymin, and pentagastrin elicited a similar increase in amylase secretion and phosphatidylinositol turnover in rat pancreatic fragments. The concentration of each secretagogue that provoked half-maximal stimulation of amylase secretion was three to six times lower than that which induced half-maximal stimulation of phosphatidylinositol turnover. The increased turnover of phosphatidylinositols due to carbamylcholine or pancreozymin, but not the secretory response, persisted in a calcium-free medium or in 90% heavy water. The replacement of the media Na+ with Li+ increased an atropine-resistant turnover of phosphatidylinositols, but did not stimulate secretion. The ionophore A-23187 (in a medium containing 2.5 mM Ca2+) and 10 mM NaF induced a high secretory response, but exerted no effect on phosphatidylinositol turnover. K+ at a 70 mM concentration provoked a phosphatidylinositol effect and hypersecretion. Secretin, vasoactive intestinal peptide, dibutyryl cAMP, dibutyryl cGMP, 8-bromo cGMP, and N2-monobutyryl cGMP stimulated amylase secretion without an increased turnover of phosphatidylinositols. It is concluded that, in the rat pancreas, the increased turnover of phosphatidylinositols was directly associated with secretagogues inducing calcium movements.

Amylases↗
PubMed1980

Effects of portacaval shunt and transposition on fatty acid and cholesterol biosynthesis in rat liver.

Male rats underwent either portacaval shunt or portacaval transposition; in both cases, sham-operated pair-fed rats served as controls. Three weeks after a portacaval shunt, fasting serum values of glucose (-35%) and cholesterol (-24%) were lower, and fasting plasma glucagon was higher (+65%). The wet weight of the liver and its total content in DNA, RNA, and protein decreased by 43, 40, 43, and 48%, respectively. The supernatant of liver obtained after centrifugation at 700 g incorporated less [1-14C]acetate (-56%) into fatty acids and less [1-14C]acetate (-94%) and [2-14C]mevalonate (-37%) into cholesterol. The activity of acetyl CoA carboxylase was reduced by 56%. The in vivo incorporation of [3H]H2O into liver fatty acids was 83% lower and that into liver cholesterol was 39% lower than in pair-fed controls. Several of the preceding parameters, including in vitro and in vivo labeling of hepatic fatty acids and cholesterol, were found to be mostly normal in rats with portacaval transposition. These data suggest that the reduction of fatty acid and cholesterol biosynthesis in the liver of rats with portacaval shunt was due to the reduction of total hepatic blood flow rather than to the diversion of portal blood constituents.

Animals↗
PubMed1979

Separation and partial characterization of new apoproteins from human plasma high density lipoproteins.

In four patients receiving parenteral fluids, human plasma high density lipoproteins were obtained by sequential ultracentrifugation and delipidated. Apoproteins were resolved by gel filtration on Sephadex G-200, DEAE-cellulose chromatography, and polyacrylamide gel electrophoresis. Sephadex-Fraction V was unusually large (11--33% compared to 3--7% in normal subjects) and was found to contain seven new apoprotein components of an apparent molecular weight (by SDS gel electrophoresis) between 8000 and 11 000. Amino acid analysis showed that all these peptides had a high glycine and arginine content and a very low content of threonine and valine. Isoelectric focusing gave isoelectric points ranging from 5.00 to 8.00. In two patients injected with L-[1-17C]-leucine, incorporation of radioactivity into these peptides gave specific activities of the same order of magnitude as apo C-II and apo C-III. IT may be postulated that these peptides increased significantly when proteins are deficient in the diet or have low levels in plasma. The structural and functional significance of these peptides remains to be determined.

Adult↗