Figure 4.

Schematic diagram depicting the sites of action of NPY from enteric neurons and endocrine PYY upon different targets in normal mouse colon mucosa. Direct activation of epithelial Y₁ receptors by NPY and PYY will inhibit epithelial anion (Cl⁻) secretion. Veratridine nonselectively stimulates all intrinsic submucosal neurons. NPY released from submucosal secretomotor neurons can autoinhibit NPY release (a Y₂ receptor-mediated effect) and also, when released from interneurons can inhibit (again via Y₂ receptors) other NANC secretomotor (e.g. VIP-ergic) neurons. Endocrine PYY may coactivate neuronal Y₂ receptors as well as the epithelial Y₁ receptors (predominant in mouse and human colon). Both mechanisms result in a sustained inhibition of epithelial Cl⁻ secretion. The NANC neurotransmitter in the final secretomotor neuron has not yet been positively identified, but it is most likely to be VIP that causes the cAMP-dependent epithelial Cl⁻ secretion.