Inhibition of food intake in the rat by cyproheptadine

Summary In a model of conditioned feeding behavior, oral administration of cyproheptadine (1–100 mg/kg), 30 min before presentation of food, produced a dose-dependent reduction of food intake in the rat (ED₅₀17 mg/kg during the 1st h of testing). This anorexic effect persisted for at least 24 h. These results provide further evidence that under certain conditions cyproheptadine, which is used as an orectic agent in man, can produce anorexia.     

Effect of vitamin A deficiency on rat hepatic and colon epoxide hydrase

Summary Rat liver microsomes and homogenized mucosal linings prepared from vitamin A-supplemented and deficient male rats were used in metabolic studies of 7-³H-styrene oxide. The colon tissue in deficient animals exhibits a significantly higher value of V_max than the same tissue from vitamin-supplemented animals. The implications of this finding in addition to our earlier observation¹⁰ is discussed in relation to colon carcinoma.Acknowledgments. This work was supported by USPHS (NIEHS) Grant RO1 ES 00336 and RO1 CA 00270 and funds from Hoffman-La Roche Foundation Research Corporation.     

Demonstration of "hydroxylase" and "epoxide hydrase" activities in preparations of nucleoli isolated from rat liver]

Aryl hydrocarbon hydroxylase (AHH) activity and epoxyde hydrase (EH) activity have been found in Rat liver nucleoli obtained from untreated (C) and methylcholanthrene (MC) pretreated Rats. Electron microscopic observations of nucleolar preparations did not reveal significant contamination either by intact nuclei or by nuclear membranes. Very low but detectable activity of NADPH cytochrome C reductase was found in the nucleoli. Nucleolar preparations revealed little AHH activity (12-18 pmoles/min/mg). AHH was inducible by MC in nuclei but not in nucleoli. The presence of EH in nucleoli was demonstrated with phenanthrene 9,10-oxide (550-620 pmoles/min/mg) and benzopyrene 4,5-oxide (92-116 pmoles/min/mg). These values were lower than those obtained using intact nuclei. The addition of TCPO (10(-4) M) inhibited EH activity.     

Effect of vitamin A deficiency on rat hepatic and colon epoxide hydrase.

Rat liver microsomes and homogenized mucosal linings prepared from vitamin A-supplemented and deficient male rats were used in metabolic studies of 7-3H-styrene oxide. The colon tissue in deficient animals exhibits a significantly higher value of Vmax than the same tissue from vitamin-supplemented animals. The implications of this finding in addition to our earlier observation 10 is discussed in relation to colon carcinoma.     

Tissue distribution and substrate specificity of an epoxide hydrase in the gypsy moth,Lymantria dispar

The stereoselectivity of the enzymatic hydration of disparlure, the pheromone for the gypsy mothLymantria dispar, and for twomeso analogues was determined. A single expoxide hydrase (EH), present in various male and female moth tissues, converted disparlure and the analogues to their respectivethreo-(R,R)-diols with high stereoselectivity as determined by analysis of the diols by chiral phase capillary gas chromatography. This EH recognizes thecis-nature of the dialkyl oxirane, but shows poor discrimination of the two alkyl chains.     

Inhibition of rat liver transglutaminase by nucleotides

Summary Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Kinetic behaviour of microsomal styrene monooxygenase and styrene epoxide hydratase in different animal species

Summary The apparent K_m and V_max values of styrene epoxide forming monooxygenase and styrene epoxide hydratase have been evaluated in the liver microsomes of male rats, mice, guinea-pigs and rabbits. Epoxide hydratase gave much higher and more uniform K_m values than the monooxygenase in the species considered.Acknowledgments. This work has been partially supported by the Fondazione Valenti (Milano). To whom enquiries should be addressed.     

The dearalkylation of fomocaine isomers by microsomal monooxygenase system of rabbit liver

Zusammenfassung Oxidative Spaltung der Äther-Bindung in Fomocain (Panacain^®) durch das mikrosomale Monooxygenase-System der Kaninchenleber wurde nachgewiesen. Aus der Kinetik dieser Dearylalkylierung wird geschlossen, dass daspara-Isomere eine doppelt so grosse Affinität zum mikrosomalen Enzymsystem besitzt als dasortho-Isomere und doppelt so schnell metabolisiert wird. Die Dearylalkylierung scheint eine allgemeine Biotransformationsreaktion für derartige strukturelle Typen zu sein.     

Inhibition of rat liver transglutaminase by nucleotides.

Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Inhibition of DNA synthesis in regenerating rat liver by hydrocortisone

Résumé Dans le foie du rat en voie de régénération, la biosynthèse de DNA est inhibée au maximum par le hydrocortisone 17–19 h après l'opération. C'est pourquoi le foie en régénération est le plus sensible au hydrocortisone s'il est injecté pendant la période de la synthèse maximale de DNA.     

Inhibition of phosphoenolpyruvate carboxykinase by 6-phosphogluconate in rat liver

Summary Various concentrations of 6-phosphogluconate inhibit rat liver phosphoenolpyruvate carboxykinase activity. 0.04 mM 6-phosphogluconate, which is the concentration found in vivo, caused a 50% inhibition of 6-phosphoenolpyruvate carboxykinase activity. 6-Phosphogluconate lowered the V_max of the enzyme and increased the concentration of phosphoenolpyruvate required to achieve one-half of the maximum velocity. The role of 6-phosphogluconate as a regulator of the coordination of fluxes through three metabolic pathways is discussed.     

Inhibition of phosphoenolpyruvate carboxykinase by 6-phosphogluconate in rat liver

Various concentrations of 6-phosphogluconate inhibit rat liver phosphoenolpyruvate carboxykinase activity. 0.04 mM 6-phosphogluconate, which is the concentration found in vivo, caused a 50% inhibition of 6-phosphoenolpyruvate carboxykinase activity. 6-Phosphogluconate lowered the Vmax of the enzyme and increased the concentration of phosphoenolpyruvate required to achieve one-half of the maximum velocity. The role of 6-phosphogluconate as a regulator of the coordination of fluxes through three metabolic pathways is discussed.     

Inhibition of microsomal Na+ K+ ATPase of the brain by extracts of Mansonia altissima]

Water extracts of the bark of Mansonia altissima var altissima inhibit the activity of the Na+, K+-ATPase of Rabbit brain microsomes. The kinetics of hydrolysis of ATP show non-competitive inhibition analogous to that produced by ouabain.     

Induction of nuclear styrene monooxygenase and epoxide hydrolase in rat liver

Summary The apparent K_m and V_max of styrene monooxygenase and styrene epoxide hydrolase were determined in intact nuclear preparations from male rat liver after in vivo treatment with phenobarbital and -naphthoflavone, which are known to induce microsomal cytochrome P-450 and cytochrome P-448 respectively. Treatment with phenobarbital does not alter the apparent K_m, but greatly increases the V_max of both nuclear styrene monooxygenase and styrene epoxide hydrolase. Almost the same pattern is observed for styrene monooxygenase after treatment with -naphthoflavone, whereas the same treatment slightly increases both the V_max and K_m value of styrene epoxide hydrolase.This work was supported by the CNR (National Research Council) Contract No. 78.02864.96 within the special program Control of Cancer Growth.     

Inhibition of rat liver adenyl cyclase by adenosine and adenine nucleotides

Riassunto L'attività adenilciclasica delle frazioni subcellulari di fegato di ratto fu inibita dall'adenosina, dall'AMP e dall'ADP (1 mM) del 60, 50 e 40%. Alla concentrazione di 0.08 mM, l'adenosina e l'AMP inibirono l'attività ciclasica del 40 e del 30%. L'IMP, l'inosina, l'adenina e l'ipoxantina furono senza effetto.

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This work was aided by Grants No. AM06034 and No. FR05641 from the National Institutes of Health, U.S. Public Health Service.     

Inhibition of rat liver glutamine synthetase by phosphonic analogues of glutamic acid

Summary Analogues of glutamic acid, -methylglutamic acid and glutamine in which the -or -COOH groups are replaced by PO₃H₂ or P(O)(OH₃)OH functions competitively inhibit rat liver glutamine synthetase. The K₁ values are comparable to or lower than K_M for L-glutamate.This study was supported by grant R.1.9.