Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3-36) on food intake.

Abstract

The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal L-cells post-prandially in proportion to calorie intake, and modulates food intake. Peripheral administration of PYY((3-36)) reduces food intake and body weight in rodents and suppresses appetite and food intake in humans. PYY((3-36)) is hypothesised to inhibit food intake via activation of the auto-inhibitory pre-synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcuate (ARC) NPY neurons. We aimed to investigate the feeding effect of PYY((3-36)) following blockade of ARC Y2R, using the specific receptor antagonist BIIE0246, in the rat. We found that pre-treatment with BIIE0246 (1 nmol) into the ARC attenuated the reduction in feeding observed following intraperitoneal injection of PYY((3-36)) (7.5 nmol/kg) (0-1 h food intake: BIIE0246/PYY((3-36)): 3.8 +/- 0.4 g; vs. Vehicle/PYY((3-36)): 2.7 +/- 0.2 g; P < 0.05). We found plasma PYY levels to be maximal at 120 min post-initiation of feeding. On investigation of the endogenous role of the Y2R, we found that ARC administration of BIIE0246 alone significantly increased feeding in satiated rats compared to vehicle-injected controls (0-1 h food intake: BIIE0246: 4.1 +/- 0.7 g; vs. vehicle: 1.7 +/- 0.7 g; P < 0.05), suggesting that Y2R antagonism disinhibits the NPY neuron thus stimulating feeding in otherwise satiated rats. These studies suggest that the Y2R plays an important role in post-prandial satiety and provide further insight into the mechanisms of action of PYY((3-36)).

• Authors: Caroline R Abbott, Caroline J Small, Adam R Kennedy, Nicola M Neary, Arshia Sajedi, Mohammad A Ghatei, Stephen R Bloom
• Journal: Brain research (Brain Res) Vol. 1043 Issue 1-2 Pg. 139-44 (May 10 2005) ISSN: 0006-8993 [Print] Netherlands
• PMID: 15862527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzazepines
• Peptide Fragments
• Receptors, Neuropeptide Y
• neuropeptide Y2 receptor
• Peptide YY
• peptide YY (3-36)
• Arginine
• BIIE 0246

Topics

• Animals
• Appetite (drug effects, physiology)
• Arcuate Nucleus of Hypothalamus (cytology, drug effects, physiology)
• Arginine (analogs & derivatives, pharmacology)
• Benzazepines (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Eating (drug effects, physiology)
• Male
• Neurons (drug effects, physiology)
• Peptide Fragments
• Peptide YY (blood, pharmacology)
• Rats
• Rats, Wistar
• Receptors, Neuropeptide Y (antagonists & inhibitors)
• Satiation (drug effects, physiology)