Related Experiment Videos
NPY receptor subtype in the rabbit isolated ileum
M Félétou1, J P Nicolas, M Rodriguez
1Institut de Recherches Servier, Suresnes, France. feletou@servier.fr
British Journal of Pharmacology
|July 13, 1999
Summary
The rabbit ileum preparation is not selective for the Neuropeptide Y (NPY) Y5 receptor. Instead, research indicates the NPY Y4 receptor subtype is responsible for inhibiting spontaneous contractions in the rabbit ileum.
Area of Science:
- Pharmacology
- Neuroscience
- Gastroenterology
Background:
- The Neuropeptide Y (NPY) system plays a crucial role in various physiological processes, including gastrointestinal motility.
- Specific NPY receptor subtypes (Y1, Y2, Y4, Y5) mediate distinct actions, and understanding their distribution is vital for therapeutic targeting.
- The rabbit ileum has been historically considered a model for studying NPY Y5 receptor activity, necessitating verification.
Purpose of the Study:
- To investigate the hypothesis that the rabbit ileum is a selective preparation for the NPY Y5 receptor.
- To characterize the NPY receptor subtype(s) involved in modulating spontaneous contractions of the rabbit isolated ileum.
- To utilize newly synthesized selective antagonists to elucidate receptor involvement.
Main Methods:
- Recording spontaneous contractions of the rabbit isolated ileum.
- Performing binding experiments in cells expressing human NPY Y1, Y2, Y4, or Y5 receptor subtypes.
- Utilizing selective NPY receptor antagonists (BIBO 3304, CGP 71683A, JCF 109) and a non-selective ligand (1229U91).
Main Results:
- NPY analogues inhibited rabbit ileum contractions with an order of potency (hPP > rPP > PYY > [Leu31,-Pro34]-NPY > NPY >> NPY13-36) that correlated with affinity for the Y4 receptor subtype, not Y5.
- Selective Y1 and Y5 receptor antagonists (BIBO 3304, CGP 71683A) did not affect the response to hPP, while another Y5 antagonist (JCF 109) showed effects only at high, intrinsically active doses.
- The non-selective ligand 1229U91 inhibited ileum contractions and the response to hPP, with an apparent pKB of 7.2, further supporting Y4 involvement.
Conclusions:
- The rabbit ileum preparation is not selective for the NPY Y5 receptor.
- The NPY Y4 receptor subtype is the primary mediator of NPY-induced inhibition of spontaneous contractile activity in the rabbit ileum.
- These findings necessitate a re-evaluation of the rabbit ileum as a model for NPY Y5 receptor research.