Role of protein kinases on acid-induced duodenal bicarbonate secretion in rats.
We examined the effect of several protein kinase inhibitors, such as staurosporine for protein kinase C (PKC), H-89 for protein kinase A (PKA) and genistein for tyrosine kinase (TK) on acid-induced duodenal bicarbonate secretion (DBS) in rats. HCO(-)(3) secretion was measured using the pH-stat method. Mucosal acidification was performed by perfusing the duodenal loop for 10 min with pH 2.2 HCl. Indomethacin, staurosporine and genistein were added to acidified saline and then perfused, respectively. In some cases, genistein and phorbol 12-myristate 13-acetate (PMA) were added to the luminal solution to examine the effect on basal duodenal HCO(-)(3) secretion. PGE(2) (PKA pathway) and PMA (PKC pathway) stimulate basal DBS. Indomethacin, H-89, staurosporine and genistein inhibit acid-induced DBS, indicating involvement of the cyclooxygenase, PKA, PKC and TK pathways.
Furukawa
Osamu
O
Greater Los Angeles Veterans Affairs Healthcare System, School of Medicine, University of California Los Angeles, Calif, USA.
Hirokawa
Masahiko
M
Guth
Paul H
PH
Engel
Eli
E
Kaunitz
Jonathan D
JD
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008297:Male; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D001639:Bicarbonates; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D015232:Dinoprostone; D006851:Hydrochloric Acid