title: Phorbol esters inhibit ammoniagenesis and gluconeogenesis in proximal tubular segments.
abstract: To characterize the regulation of ammoniagenesis and gluconeogenesis in renal proximal tubule, ammonia and glucose productions were measured in suspensions of canine proximal tubular segments incubated with 10 mM L-glutamine. Productions were linear functions of time for 120 min and were decreased as extracellular pH was increased from 7.0 to 7.5 To ascertain whether activation of protein kinase c affects either process, we incubated segments with tumor-promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate (TPA), or phorbol 12,13-dibutyrate, or with the inactive phorbol ester 4 alpha-phorbol. Ammoniagenesis and gluconeogenesis were inhibited by incubation with 10(-6) M of the two former compounds but not the latter compound. Inhibition of ammoniagenesis and gluconeogenesis occurred after incubation with as little as 10(-9) M phorbol 12,13-dibutyrate. Phorbol ester-induced inhibition was observed under conditions such that extracellular [Na+] was greater than intracellular [Na+], but not when extracellular [Na+] equaled intracellular [Na+], and was not observed in the presence of amiloride. Our findings are consistent with a role for protein kinase c in the control of ammoniagenesis and gluconeogenesis in proximal tubule. Such control could be mediated via stimulation of Na+-H+ exchange.
authors.forename: M C
authors.initials: MC
authors.lastname: Chobanian
authors.forename: M R
authors.initials: MR
authors.lastname: Hammerman
mesh_terms: D000641:Ammonia / Q000096:biosynthesis*; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D005943:Gluconeogenesis / Q000187:drug effects*; D005973:Glutamine / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; D010704:Phorbols; D005973:Glutamine; D015240:Phorbol 12,13-Dibutyrate; D000641:Ammonia; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol; D004121:Dimethyl Sulfoxide