Effects of peptide YY and its analogues on chloride ion secretion in fed and fasted rat jejunum.

Abstract The aim of our study was to determine whether a meal modifies the antisecretory response induced by PYY and the structural requirements to elicit antisecretory effects of analogue PYY(22–36) for potential antidiarrhea therapy. The variations in short-circuit current (Isc) due to the modification of ionic transport across the rat intestine were assessed in vitro, using Ussing chambers. In fasted rats, PYY induced a dose- and time-dependent reduction in Isc, with a sensitivity threshold at 5 × 10 −11 M (ΔIsc −2 ± 0.5 μ A/cm 2 ). The reduction was maximal at 10 −7 M (Isc −23 ± 2 μA/cm 2 ), and the concentration producing half-maximal inhibition was 10 −9 M . At 10 −7 M , reduction of Isc by PYY reached 90% of response to 5 × 10 −5 M bumetanide. The PYY effect was partly reversed by 10 −5 M forskolin (Isc +13.43 ± 2.91 μA/h·cm 2 , p −3 M dibutyryl adenosine 3′,5′ cyclic monophosphate (Isc +12 ± 1.69 μA/cm 2 , p 2 ( p C -terminal fragment (22–36) and an aromatic amino acid residue (Trp or Phe) at position 27. At 10 −7 M the biological activity of PYY was lower in fed than fasted rats ( p