Protein kinase C mediates the inhibitory effect of substance P on HCO3- secretion from guinea pig pancreatic ducts

被引:24
作者
Hegyi, P
Rakonczay, Z
Tiszlavicz, L
Varró, A
Tóth, A
Rácz, G
Varga, G
Gray, MA
Argent, BE
机构
[1] Newcastle Univ, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Univ Szeged, Fac Med, Dept Med 1, Szeged, Hungary
[3] Univ Szeged, Fac Med, Dept Pathol, Szeged, Hungary
[4] Univ Szeged, Fac Med, Dept Pharmacol & Pharmacotherapy, Szeged, Hungary
[5] Hungarian Acad Sci, Dept Oral Biol, Mol Oral Biol Res Grp, Budapest, Hungary
[6] Semmelweis Univ, H-1085 Budapest, Hungary
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2005年 / 288卷 / 05期
关键词
pancreas; Cl-/; HCO3-; exchanger; inhibition; epithelium;
D O I
10.1152/ajpcell.00430.2003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The inhibitory control of pancreatic ductal HCO3- secretion may be physiologically important in terms of limiting the hydrostatic pressure developed within the ducts and in terms of switching off pancreatic secretion after a meal. Substance P (SP) inhibits secretin-stimulated HCO3- secretion by modulating a Cl--dependent HCO3- efflux step at the apical membrane of the duct cell (Hegyi P, Gray MA, and Argent BE. Am J Physiol Cell Physiol 285: C268-C276, 2003). In the present study, we have shown that SP is present in periductal nerves within the guinea pig pancreas, that PKC mediates the effect of SP, and that SP inhibits an anion exchanger on the luminal membrane of the duct cell. Secretin (10 nM) stimulated HCO3- secretion by sealed, non-perfused, ducts about threefold, and this effect was totally inhibited by SP (20 nM). Phorbol 12,13-dibutyrate (PDBu; 100 nM), an activator of PKC, reduced basal HCO3- secretion by similar to 40% and totally blocked secretin-stimulated secretion. In addition, bisindolylmaleimide I (1 nM to 1 mu M), an inhibitor of PKC, relieved the inhibitory effect of SP on secretin-stimulated HCO3- secretion and also reversed the inhibitory effect of PDBu. Western blot analysis revealed that guinea pig pancreatic ducts express the alpha-, beta(I)-, delta-, epsilon-, eta-, theta-, zeta-, and mu-isoforms of PKC. In microperfused ducts, luminal H2DIDS (0.5 mM) caused intracellular pH to alkalinize and, like SP, inhibited basal andsecretinstimulated HCO3- secretion. SP did not inhibit secretion further when H2DIDS was present in the lumen, suggesting that SP and H2DIDS both inhibit the activity of an anion exchanger on the luminal membrane of the duct cell.
引用
收藏
页码:C1030 / C1041
页数:12
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