SODIUM-FLUORIDE INHIBITS THE ANTISECRETORY EFFECT OF PEPTIDE YY AND ITS ANALOG IN RABBIT JEJUNUM

The antisecretory peptide YY(PYY) inhibits jejunal secretion through a nd inhibitory protein (Gi), whereas sodium fluoride (NaF) is a potent activator of G-proteins. G-proteins. This work was conducted to charac terize the role of NaF in the antisecretory effect of PPY. For this pu rpose, electrogenic chloride secretion was assessed by measuring the i n vitro variations in short-circuit current (Delta Isc) due to alterat ions in ionic transport, using Ussing chambers. Results: 1) NaF induce d a transient increase in Isc at concentrations exceeding 5 mM. 2) 2 m M NaF inhibited the antisecretory effect of 0.1 mu M PYY and of its an alog P915. 3) stimulation of secretion by forskolin and dbcAMP was hal ved in the presence of 2 mM NaF. 4) Inhibition of protein kinase C by 0.1 mM bisindolylmaleimide caused a sustained increase in Isc in the p resence of 5 mm NaF. In conclusion, these results confirm that PYY inh ibits electrogenic chloride secretion and show that NaF stimulates it, and suggest that NaF reduces PYY-induced inhibition via. a G-dependen t and a G-independent functional pathway.