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Phorbol esters inhibit ammoniagenesis and gluconeogenesis in proximal tubular segments

Journal Article · · Am. J. Physiol.: Heart Circ. Physiol.; (United States)
OSTI ID:6201295

To characterize the regulation of ammoniagenesis and gluconeogenesis in renal proximal tubule, ammonia and glucose productions were measured in suspension 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, the authors 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..cap alpha..-phorbol. Ammoniagenesis and gluconeogenesis were inhibited by incubation with 10/sup /minus/6/M of the two former compounds but not the latter compound. Phorbol ester-induced inhibition was observed under conditions such that extracellular (Na/sup +/) was greater than intracellular (Na/sup +/), but not when extracellular (Na/sup +/) equaled intracellular (Na/sup +/), and was not observed in the presence of amiloride. These 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/sup 1/-H/sup +/ exchange.

Research Organization:
Washington Univ. School of Medicine, St. Louis, MO (USA)
OSTI ID:
6201295
Journal Information:
Am. J. Physiol.: Heart Circ. Physiol.; (United States), Journal Name: Am. J. Physiol.: Heart Circ. Physiol.; (United States) Vol. 21:6; ISSN AJPPD
Country of Publication:
United States
Language:
English