title: Purinergic regulation of glucose and glutamine synthesis in isolated rabbit kidney-cortex tubules.
abstract: The effects of extracellular purinergic agonists and their breakdown products on glucose and glutamine synthesis in rabbit kidney-cortex tubules incubated with aspartate + glycerol or alanine + glycerol + octanoate were investigated. A rapid extracellular degradation of ATP was accompanied by an accumulation of AMP, inosine, and hypoxanthine. Extracellular ATP and its breakdown products accelerated glucose synthesis in renal tubules, while ammonium released from adenine-containing compounds enhanced glutamine synthesis and diminished the degree of gluconeogenesis stimulation. In contrast to AMP and inosine, ATP evoked calcium signals, while both ATP and inosine decreased intracellular cAMP content and accelerated the flux through fructose-1,6-bisphosphatase as concluded from changes in gluconeogenic intermediates. Since (i) the activity of partially purified renal fructose-1,6-bisphosphatase was increased upon protein phosphatase-1 treatment and decreased following treatment of previously dephosphorylated enzyme with protein kinase A catalytic subunit and (ii) both 8-bromoadenosine 3',5'-cyclic monophosphate and 8-(4-chlorophenyltio)-cAMP inhibited renal glucose synthesis, it seems likely that in rabbit renal tubules ATP and inosine stimulate gluconeogenesis via cAMP decrease, which favors the appearance of a more active, dephosphorylated form of fructose-1,6-bisphosphatase, a key gluconeogenic enzyme.
authors.affiliation: Department of Metabolism Regulation, Institute of Biochemistry, Warsaw University, Warsaw 02-096, Poland.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Jagielski
authors.forename: Dagmara
authors.initials: D
authors.lastname: Wohner
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Lietz
authors.forename: Robert
authors.initials: R
authors.lastname: Jarzyna
authors.forename: Rafał A
authors.initials: RA
authors.lastname: Derlacz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Winiarska
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Bryła
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000409:Alanine / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis*; D005973:Glutamine / Q000096:biosynthesis*; D005990:Glycerol / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D008297:Male; D010766:Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008024:Ligands; D000643:Ammonium Chloride; D005973:Glutamine; D019271:Hypoxanthine; D001224:Aspartic Acid; D000249:Adenosine Monophosphate; D007288:Inosine; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006597:Fructose-Bisphosphatase; D005947:Glucose; D000241:Adenosine; D000409:Alanine; D005990:Glycerol