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NEUROREGULATION AND MOTILITY

Physiological role of neuropeptide Y in the regulation of the ascending phase of the peristaltic reflex

Department of Physiology and Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298

Submitted 18 February 2003 ; accepted in final form 26 July 2003

The physiological role of neuropeptide Y (NPY) and of specific NPY receptors in regulating the intestinal peristaltic reflex was examined in three-compartment flat-sheet preparations of rat colon. Graded muscle stretch or mucosal stimulation applied to the central compartment inhibited NPY release in the orad compartment where ascending contraction was measured. NPY and the Y₁-receptor agonist [Leu³¹, Pro³⁴]NPY inhibited, whereas the selective Y₁-receptor antagonist BIBP 3226 augmented ascending contraction and substance P (SP) release in the orad compartment induced by muscle stretch or mucosal stimulation. Neither agonist nor antagonist had any effect on descending relaxation or VIP release in the caudad compartment. The Y₂-receptor agonist NPY_13-36 and antagonist BIIE 0246 had no effect on peptide release or mechanical response. The results indicate that suppression of a tonic inhibitory influence of NPY neurons on excitatory neurotransmitter release contributes substantially to the orad contractile phase of the peristaltic reflex. The effect of NPY on neurotransmitter release is mediated by Y₁ receptors.

enteric nervous system; tachykinins; NPY receptors; colon

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