title: Hyperammonaemia in V1a vasopressin receptor knockout mice caused by the promoted proteolysis and reduced intrahepatic blood volume.
abstract: An analysis of arginine-vasopressin (AVP) V1a receptor-deficient (V1aR-/-) mice revealed that glucose homeostasis and lipid metabolism were altered in the mutant mice. Here, we used V1aR-/- mice to investigate whether the deficiency of the V1a receptor, which led to altered insulin sensitivity, affected protein metabolism. The serum 3-methylhistidine levels were increased in V1aR-/- mice under feeding conditions, indicating that proteolysis was enhanced in muscle tissue from V1aR-/- mice. Furthermore, serum amino acid profiling revealed that the amino acid levels, including glycogenic and branched-chain amino acids, were reduced in V1aR-/- mice. In addition, an alanine-loading test showed that gluconeogenesis was enhanced in V1aR-/- mice. Blood ammonia, which is a by-product of amino acid catabolism, was two times higher in V1aR-/- mice without hepatopathy under the feeding and fasting conditions than in wild-type mice. Amino acid profiling also revealed that the amino acid pattern was not typical of a urea-cycle enzymatic disorder. An ammonia tolerance test and an indocyanine green elimination test showed that V1aR-/- mice had lower ammonia clearance due to a decreased intrahepatic circulating blood volume. Metabolic acidosis, including lactic- and keto-acidosis, was not observed in V1aR-/- mice. These results provide evidence that proteolysis promotes the production of glucose in the muscles of V1aR-/- mice and that hyperammonaemia is caused by promoted protein catabolism and reduced intrahepatic blood volume. Thus, our study with V1aR-/- mice indicates that AVP plays a physiological role via the V1a receptor in regulating both protein catabolism and glucose homeostasis.
authors: Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
authors: Masami
authors: M
authors: Hiroyama
authors: Toshinori
authors: T
authors: Aoyagi
authors: Yoko
authors: Y
authors: Fujiwara
authors: Sayuri
authors: S
authors: Oshikawa
authors: Atsushi
authors: A
authors: Sanbe
authors: Fumio
authors: F
authors: Endo
authors: Akito
authors: A
authors: Tanoue
mesh_terms: D000596:Amino Acids / Q000097:blood; D000641:Ammonia / Q000097:blood / Q000378:metabolism; D000643:Ammonium Chloride / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001810:Blood Volume; D002245:Carbon Dioxide / Q000097:blood; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D022124:Hyperammonemia / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007657:Ketone Bodies / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation; D008762:Methylhistidines / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007657:Ketone Bodies; D008762:Methylhistidines; D011506:Proteins; D017483:Receptors, Vasopressin; D000643:Ammonium Chloride; D001127:Arginine Vasopressin; D002245:Carbon Dioxide; D019344:Lactic Acid; D000641:Ammonia; D010447:Peptide Hydrolases; D005947:Glucose; C028118:3-methylhistidine