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Research Article

Peripheral peptide YY inhibits propulsive colonic motor function through Y₂ receptor in conscious mice

¹UCLA ^{2 3}VA West Los Angeles Medical Center\ ⁴UCLA - Center for Neurobiology of Stress ⁵Center for Neurovisceral Sciences

Submitted 24 August 2009 ; revision received 16 October 2009 ; accepted in final form 2 November 2009

ABSTRACT

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established while less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY_3-36, PYY and neuropeptipde Y (NPY) (8 nmol/kg) injected intraperitoneally (ip) inhibited fecal pellet output (FPO)/h during novel environment stress by 90%, 63% and 57% respectively while the Y₁ preferring agonists, [Pro³⁴]PYY and [Leu³¹,Pro³⁴]NPY had no effect. Corticotrophin-releasing factor 2 receptor antagonist did not alter PYY_3-36 inhibitory action. PYY and PYY_3-36 significantly reduced restraint-stimulated defecation, and PYY_3-36 inhibited high amplitude distal colonic contractions as recorded in restrained conscious mice for 1 h recorded by intraluminal pressure using a microtransducer. PYY suppression of 5-hydroxytryptophan (5-HTP, ip)-induced FPO and diarrhea was blocked by Y₂ antagonist, BIIE0246, injected ip and mimicked by PYY_3-36 but not [Leu³¹, Pro³⁴]NPY. PYY_3-36 also inhibited bethanechol-stimulated FPO and diarrhea. PYY_3-36 inhibited basal FPO during nocturnal feeding period and light phase in fasted/refed mice for 2-3 h while the reduction of food intake lasted only for 1 h. PYY_3-36 delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104% while [Leu³¹,Pro³⁴]NPY had no effect. In the proximal and distal colon, higher Y₂ mRNA expression was detected in the mucosa than muscle layers and Y₂ immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY_3-36 potently inhibits basal and stress/5-HT/cholinergic stimulated propulsive colonic motor function in conscious mice likely via Y₂ receptors.

PYY3-36; stress; serotonin; bethanechol