Neuropeptide Y Receptor Modulators in Gut Physiology and Therapy

Area of Science:

• Neurogastroenterology
• Peptide Signaling
• Gastrointestinal Physiology

Background:

• The gut-brain axis relies on neuropeptides like Neuropeptide Y (NPY) for communication.
• NPY family peptides (NPY, PYY, PP) regulate gastrointestinal (GI) motility, secretion, nutrient absorption, and development.
• Disruptions in NPY signaling are implicated in GI diseases such as IBS, IBD, gastroparesis, and obesity.

Purpose of the Study:

• To review the physiological and pathological roles of NPY and its receptor subtypes (Y1, Y2, Y4, Y5) in the GI tract.
• To evaluate the therapeutic potential of pharmacological and natural modulators targeting the NPY pathway.
• To explore NPY modulation's clinical implications in gastrointestinal health and disease.

Main Methods:

• Comprehensive review of experimental, clinical, and pharmacological evidence.
• Analysis of receptor-specific activities and underlying pathophysiology.
• Investigation of clinical implications of NPY modulation in GI disorders.

Main Results:

• NPY signaling influences GI motility, secretion, and appetite through various receptor pathways.
• Low NPY levels correlate with diarrhea in IBD; PYY promotes nutrient absorption via the ileal brake.
• Targeting Y1 receptors shows potential for treating diarrhea (agonists) and constipation (antagonists); Y2/Y5 modulators may help with obesity and gastroparesis.

Conclusions:

• NPY receptors are integral to GI homeostasis and disease.
• Precision-based pharmacological interventions targeting NPY receptors enhance understanding of receptor interactions.
• Further research with robust study designs and long-term data is needed to fully realize therapeutic potential.