PYY Inhibition of VIP-Stimulated Ion Transport in the Rabbit Distal Ileum

Autor: James R. Goldenring, Irvin M. Modlin, Garth H. Ballantyne, Susan A. Sgambati, L. Peter Fielding, Marc D. Basson, Jacquelyn A. Quin
Rok vydání: 1995
Předmět:
Zdroj: Journal of Surgical Research. 58:111-115
ISSN: 0022-4804
DOI: 10.1006/jsre.1995.1018
Popis: Vasoactive intestinal polypeptide (VIP) is the pathophysiologic mediator of several small intestinal hypersecretion states. VIP exerts its effect by binding mucosal receptors and ultimately increasing intracellular levels of cAMP. Peptide YY (PYY), a GI hormone concentrated in the distal ileum and colon, has been demonstrated to decrease VIP-mediated secretion in the colon through a specific Y4 mucosal receptor. Characterization of PYY's effect on VIP-stimulated small intestinal secretion may provide a basis for future therapeutic interventions. We hypothesized that ion transport in the small intestine is mediated through a novel Y receptor subtype. We performed Ussing chamber ion transport studies on rabbit ileum using VIP, PYY, and other pancreatic polypeptide (PP)-fold peptides in order to specifically examine: (1) the effects of VIP and PYY on basal and VIP-stimulated short circuit current (I sc ), and (2) the changes in VIP-stimulated I sc in response to NPY, PP, leucine 31 ,proline 31 neuropeptide Y fragment, ([Leu 31 ,Pro 31 ]NPY) and the carboxy-terminal fragment of NPY (NPY 13-36 ). VIP increased basal I sc in a concentration-dependent manner, while PYY decreased basal I sc . Graded concentrations of PYY decreased VIP-stimulated increases in I sc . PYY added prior to VIP had no effect on VIP-stimulated increases in I SC . Inhibition of VIP-stimulated I sc increases was seen with NPY, but not with [Leu 31 ,Pro 34 ]NPY, PP, or NPY 13-36 . This distinct pattern of binding affinity characterizes a novel Y receptor subtype. Additionally, increases in I sc by VIP despite pretreatment with PYY suggests that VIP-stimulated ion transport is mediated through mechanisms other than increases in cAMP
Databáze: OpenAIRE