Role of protein kinase C in duodenal mucosal bicarbonate secretion in the guinea pig.
Since duodenal bicarbonate secretion (DBS) is increased by m-cholinoceptor agonists, it was postulated that protein kinase C (PKC) has a role in this secretion. This premise was examined in guinea pigs, using 12-O-tetradecanoyl-phorbol 13-acetate (TPA) to stimulate bicarbonate production in the perfused duodenum in vivo, and to activate PKC in isolated duodenal enterocytes. TPA (10(-7) mol.kg-1) infused intravenously stimulated active DBS from basal values of 3.64 +/- 0.66 to 8.73 +/- 1.59 mumol.cm-1.10 min-1. This effect was completely blocked by verapamil (4 x 10(-7) mol.kg-1). PKC activity in duodenal enterocytes in the basal state was most abundant in the cytosolic fraction (2,221 +/- 444 U/mg protein) and very low in the particulate fraction (227 +/- 51 U/mg protein). TPA (10(-7) mol.kg-1) caused a time-dependent translocation of the cytosolic, lipid-dependent activity of PKC into the particulate fraction. The effect was maximal at 5 min incubation and was reversed by 30 min. In the particulate fraction, this activity was no longer lipid-dependent, but could be stimulated by Ca2+ alone. These data support the hypothesis that translocation of PKC may contribute to DBS.
Odes
H S
HS
Gastroenterology Institute, Soroka Medical Center, Beer Sheva, Israel.
Reimer
R
R
Muallem
R
R
Schwenk
M
M
Beil
W
W
Sewing
K F
KF
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008055:Lipids / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D001639:Bicarbonates; D008055:Lipids; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate