COMPARISON OF THE ANTISECRETORY EFFECT OF ENDOGENOUS FORMS OF PEPTIDEYY ON FED AND FASTED RAT JEJUNUM

It is intriguing that the antisecretory peptide YY is present in plasm a in two forms: PYY1-36 and PYY3-36. PYY3-36 has been found in human a nd rabbit blood within 30 min of the beginning of the meal, when the p eak of water and electrolyte secretion occurs in the duodeno-jejunum, The aim of this study was therefore to compare the antisecretory effec t of PYY1-36 and PYY3-36 in fed and fasted rat jejunum. The variations in electrolyte secretion were assessed by measuring the variations in short-circuit current (Delta Isc) and transepithelial isotopic chlori de fluxes in jejunal mucosa isolated from fed and fasted animal, and m ounted in Ussing Chambers. In fasted animals, 2 x 10(-7) M PYY3-36 ind uced a reduction in Isc of -0.50 +/- 0.01 mu Eq/hr.cm(2), which was no t statistically different from that induced by x 10(-7) M PYY1-36 (-0. 60 +/- 0.01 mu Eq/h cm(2)). In contrast, in fed animals, 2 x 10(-7) M PYY3-36 did not trigger a significant response on Isc and net chloride flux, while the response to PYY1-36 was present but blunted. The abse nce of response was probably not related to the presence of secretory peptides because PYY3-36 was still able to induce a reduction in Isc a fter stimulation by a series of 10 different secretory peptides. After 10(-8) M PYY3-36 addition to an epithelium from the fasted animal, re sponse to 10(-7) M PYY3-36 was blunted for 30 min and returned to cont rol value after GO min. Plasma concentration of PYY was higher in the fed rats compared to fasted (213.78 +/- 35 vs. 53.62 +/- 11.47 pg/ml p < 0.01). After incubation of crypt cells with or without 0.1 mu M of unlabeled PYY for 60 min, Scatchard analysis of equilibrium binding da ta show that binding capacity (B-max) of receptors was reduced when cr ypt cells were previously incubated with unlabeled PYY without signifi cant modification of dissociation constants. B-max were 183 +/- 27 in control vs. 56 +/- 11 fmol/mg protein. These results confirm the antis ecretory activity of PYY1-36 in the jejunum of fasted and fed rats. Th ey further indicate that PYY3-36 displays similar activity to PYY1-36 in fasted animals, but lack of activity in fed animals. These results suggest that the two circulating forms of PYY act as antisecretory pep tide by two different mechanisms, implying a C-terminal specificity. ( C) 1997 Elsevier Science Inc.