Rapid stimulation of Na<sup>+</sup>,K<sup>+</sup>‐ATPase by glucagon, epinephrine, vasopressin and cAMP in perfused rat liver

Radomińska-Pyrek, A; Kraus‐Friedmann, Naomi; Lester, Roger; Little, Joanna M.; Denkins, Yvonne

doi:10.1016/0014-5793(82)80015-x

Cited by 25 publications

(16 citation statements)

References 15 publications

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“…Recent preliminary work has confirmed our previous observations on HDC and has identified another 6ahydroxylated bile acid, hyocholic acid (3a,6a,7a-trihydroxy), as an excellent substrate for hepatic microsomal UDPglucuronyltransferase with kinetic parameters resembling those described herein [36].…”

Section: Fig 3 Lineweaver and Burk Plots Of 6a-hydroxylated Bile Acsupporting

confidence: 86%

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

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Pessah

Sacquet

et al. 1988

European Journal of Biochemistry

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The glucuronidation of bile acids is an established metabolic pathway in different human organs. The hepatic and renal UDP-glucuronyltransferase activities vary according to the bile acids concerned. Thus, hyodeoxycholic acid is clearly differentiated from other bile acids by its high rate of glucuronidation and elevated urinary excretion in man. To determine whether such in vivo observations are related to variations in bile acid structure, human hepatic and renal microsomes were prepared and time courses of bile acid glucuronidation measured with the bile acids possessing hydroxyl groups in different positions. Eleven [24-14C]bile acids were chosen or synthesized in respect of their specific combination of hydroxyl and 0x0 groups at the 3,6, 7 and 12 positions and of their c1 or 8 hydroxyl configurations. The results clearly demonstrate that bile acids with an hydroxyl group in the 6a position underwent a high degree of glucuronidation. Apparent kinetic K, and V,,, values for UDPglucuronyltransferase activities ranged over 78 -66 pM and 1.8 -3.3 nmol . min-' . mg-protein in the liver and over 190-19 pM and 0.5-9.2 nmol . min-' . mg-' protein in the kidney. All the other bile acids tested, each of which possessed a 3a-hydroxyl group and whose second or third hydroxyl was bound at the 68, 7 or 12 positions, were glucuronidated to a degree far below that of the 6a-hydroxylated bile acids. We conclude that an active and highly specific UDP-glucuronyltransferase activity for 6a-hydroxylated bile acids exists in human liver and kidneys. Moreover, this activity results in the linkage of glucuronic acid to the 6a-hydroxyl group and not to the usual 3a-hydroxyl group of bile acids.Biliary and urinary excretion of endogenous or exogenous substances usually require preliminary biosynthesis of more polar metabolites. Hepatic transferases play a major role in such processes by linking several chemical groups such as sulfate, glycine, taurine, glucuronic acid to a wide variety of compounds.UDP-glucuronyltransferase is able to transfer the activated form of glucuronic acid (uridine 5'-diphosphoglucuronic acid) to a large variety of xenobiotics: phenolic and naphtholic derivatives, morphine, chloramphenicol, 4-methylumbelliferone etc., as well as endogenous compounds such as bilirubin, thyroxine, and other thyroid hormones (for review see [I] Abbreviations. HDC, hyodeoxycholic acid (3a,6a-dihydroxy-58-cholan-24-oic acid) ; CDC, chenodeoxycholic acid (3~,7a-dihydroxy-5/l-cholan-24-oic acid); UDC, ursodeoxycholic acid (3a,7p-dihydroxy-5P-cholan-24-oic acid); C, cholic acid (3a,7a,12cr-trihydroxy-5/3-cholan-24-oic acid); P-MC, P-muricholic acid (3cc,6~,7P-trihydroxy-5P-cholan-24-oic acid), w-MC, w-muricholic acid (3a,6cr,7~-trihydroxy-5P-cholan-24-oic acid); 3~6 1 , 3a,6P-dihydroxy-5~-cholan-24-oic acid; 3b6a, 3P,6a-dihydroxy-5fi-cholan-24-oic acid ; 3a6-oxo,3a-hydroxy-6-oxo-5~-cholan-24-oic acid ; 3-0x0-6a, 3-oxo-6a-hydroxy-5~-cholan-24-oic acid; allo-3a6-0x0, 3a-hydroxy-6-oxo-5a-cholan-24-oic acid; Me&, trimethylsilyl.Enzyme. ...

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Section: Fig 3 Lineweaver and Burk Plots Of 6a-hydroxylated Bile Acsupporting

confidence: 86%

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

Parquet

Pessah

Sacquet

et al. 1988

European Journal of Biochemistry

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“…The reaction was allowed to proceed for 15 min at 37°C and then quenched by the addition of ice-cold 8% perchloric acid. Samples were centrifuged, and the inorganic phosphate levels were measured using the method of Radominski-Pyret et al (18). Samples to which protein was added after the reaction was terminated were used as blanks.…”

Section: Methodsmentioning

confidence: 99%

Oral Vanadate Reduces Na+-Dependent Glucose Transport in Rat Small Intestine

Madsen

Porter²,

Fedorak³

1993

Diabetes

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The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport capacity in both diabetic and control animals. In jejunum tissue, this decrease in glucose absorption was a direct consequence of downregulation of the glucose carrier and was not related to changes in mucosal morphometry. In the ileum tissue of control animals, the vanadate-induced decrease in glucose maximal transport capacity occurred in conjunction with an increase in carrier affinity and mucosal morphometric measurements. In the ileum tissue of diabetic animals, the vanadate-induced decrease in glucose maximal transport capacity occurred with a decrease in mucosal morphometric measurements. Na(+)-K(+)-adenosine triphosphatase activity was affected by vanadate only in diabetic animals. These results demonstrate that oral vanadate supplementation results in downregulation of the small intestinal sodium-dependent glucose carrier in both diabetic and nondiabetic rats. Furthermore, the vanadate effect may be occurring at the cellular level.

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“…The reaction was allowed to proceed for 15 min at 37°C and then quenched by the addition of ice-cold 8% perchloric acid. Samples were centrifuged, and inorganic phosphate levels were measured using the method of Radominski-Pyret et al (1982). Samples to which protein was added after the reaction was terminated were used as blanks.…”

Section: Na-k Atpase Activitymentioning

confidence: 99%

Insulin downregulates diabetic-enhanced intestinal glucose transport rapidly in ileum and slowly in jejunum

Madsen¹,

Ariano²,

Fedorak³

1996

Can. J. Physiol. Pharmacol.

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The effect of insulin on intestinal sodium-dependent glucose transport and brush border membrane surface area was examined in male Sprague-Dawley rats following a 30-day period of nontreated streptozocin-induced diabetes. Nontreated diabetic rats were hyperglycemic and demonstrated increased jejunal and ileal Na-dependent glucose transport Jmax (maximal transport capacity) and Na-K ATPase activity compared with controls. Daily administration of insulin resulted in a steady decline in blood glucose levels over a period of 6 days. Jejunal Jmax was normalized after 2 days of insulin therapy, while ileal Jmax was normalized 12 h following a single insulin injection. The normalization of Na-K ATPase activity lagged behind Na-dependent glucose transport regulation by 24 h in both jejunum and ileum. Brush border surface area was increased in the ileum of diabetic rats as a result of an increase in microvillus height. Insulin treatment resulted in a decrease in ileal microvillus height to control values by 12 h, which correlated directly with the decrease in Na-dependent glucose transport. Insulin had no effect on jejunal brush border surface area. In conclusion, these findings indicate that the jejunum and ileum respond differentially to experimentally induced diabetes, and these regions also utilize different adaptive mechanisms to regulate Na-dependent glucose transport.

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Rapid stimulation of Na⁺,K⁺‐ATPase by glucagon, epinephrine, vasopressin and cAMP in perfused rat liver

Cited by 25 publications

References 15 publications

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

Oral Vanadate Reduces Na+-Dependent Glucose Transport in Rat Small Intestine

Insulin downregulates diabetic-enhanced intestinal glucose transport rapidly in ileum and slowly in jejunum

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Rapid stimulation of Na+,K+‐ATPase by glucagon, epinephrine, vasopressin and cAMP in perfused rat liver

Cited by 25 publications

References 15 publications

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

Effective glucuronidation of 6α‐hydroxylated bile acids by human hepatic and renal microsomes

Oral Vanadate Reduces Na+-Dependent Glucose Transport in Rat Small Intestine

Insulin downregulates diabetic-enhanced intestinal glucose transport rapidly in ileum and slowly in jejunum

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Rapid stimulation of Na⁺,K⁺‐ATPase by glucagon, epinephrine, vasopressin and cAMP in perfused rat liver