Pathways and receptors involved in peptide YY induced contraction of rat proximal colonic muscle in vitro

Background-Peptide YY (PYY) is involved in the regulation of several gut fu nctions, including secretion and motility. It exerts its effects through a family of six receptors, commonly named the Y receptor family. Aims-To characterise the effects of PYY on strips of rat proximal colon in vitro, and to determine the pathways and receptors involved. Methods-Contractions of strips removed from the muscle layer of rat proxima l colon were recorded under isometric conditions, using PYY, Y receptor ago nists and antagonists, and nerve blockers. Reverse transcription-polymerase chain reaction was also performed to detect the presence of mRNA coding fo r Y receptors. Finally, smooth muscle cells were isolated to estimate the c ell length and intracellular Ca2+ concentration in the presence and absence of PYY. Results-PYY, neuropeptide Y a (NPY), pancreatic polypeptide (PP) and [Leu31 ,Pro34]NPY induced a dose dependent contraction of strips from proximal col on. Tetrodotoxin partially inhibited the PW and NPY induced contractions, a nd strongly inhibited the PP induced contraction. Specific antagonists show ed the involvement of cholinergic nicotinic receptors and NK1 receptor. BIB P 3226, a specific Y1 antagonist, did not modify the colonic smooth muscle response to PYY, whereas blocking L-type Ca2+ channels with D-600 abolished its effects. Moreover, PYY induced an increase in intracellular Ca2+ conce ntration, associated with a reduction in cell length. mRNA encoding Y1 and Y4 receptors were detected in the muscle strips. Conclusions-These findings suggest that PW stimulates colonic contractile a ctivity in vitro through (a) a nervous Y4 dependent pathway and (b) a pathw ay involving a potential new receptor on myocytes.