Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa.
A functional study has been performed to characterise the Y receptors responsible for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations. Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln(23)hPP and rPP were effective but less potent than full length PYY, NPY or their Pro(34)-substituted analogues, while the Y(5) agonist Ala(31), Aib(32)hNPY was the least active peptide tested. The Y(1) antagonists, BIBP3226 and BIBO3304 virtually abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y(2) antagonist, BIIE0246. A combination of BIBO3304 and BIIE0246 also partially attenuated hPP responses, leaving residual effects that were most probably Y(4)-mediated. Thus we conclude that Y(1), Y(2) and Y(4) receptors attenuate ion secretion in mouse colon.
Cox
H M
HM
Centre for Neuroscience, King's College London, GKT School of Biomedical Sciences, Guy's Campus, SE1 9RT, London, United Kingdom. helen.m.cox@kcl.ac.uk
Pollock
E L
EL
Tough
I R
IR
Herzog
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001667:Binding, Competitive; D003001:Cloning, Molecular; D003106:Colon / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D017136:Ion Transport; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000737:chemistry*
C092926:BIBP 3226; D017476:Receptors, Neuropeptide Y; D010191:Pancreatic Polypeptide; D001120:Arginine; C117416:BIBO 3304