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

Abstract

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established, whereas less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal function and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY(3-36), PYY, and neuropeptide Y (NPY) (8 nmol/kg) injected intraperitoneally inhibited fecal pellet output (FPO) per hour during novel environment stress by 90%, 63%, and 57%, respectively, whereas the Y(1)-preferring agonists, [Pro(34)]PYY and [Leu(31),Pro(34)]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 in restrained conscious mice for 1 h, by intraluminal pressure with the use of a microtransducer. PYY suppression of intraperitoneal 5-hydroxytryptophan induced FPO and diarrhea was blocked by the Y(2) antagonist, BIIE0246, injected intraperitoneally and mimicked by PYY(3-36), but not [Leu(31),Pro(34)]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, whereas the reduction of food intake lasted for only 1 h. PYY(3-36) delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104%, whereas [Leu(31),Pro(34)]NPY had no effect. In the proximal and distal colon, higher Y(2) mRNA expression was detected in the mucosa than in muscle layers, and Y(2) immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY(3-36) potently inhibits basal and stress/serotonin/cholinergic-stimulated propulsive colonic motor function in conscious mice, likely via Y(2) receptors.

The short chain fatty acids, butyrate and propionate, have differential effects on the motility of the guinea pig colon

“…The inhibitory effect of SCFA, especially propionate, may be attributable to the release of peptide YY (PYY) from enteroendocrine cells. PYY has long been known to inhibit colonic propulsive motility . PYY and FFAR2 receptors are co‐expressed in enteroendocrine cells and cell lines .…”

Gut feedback mechanisms and food intake: a physiological approach to slow carbohydrate bioavailability

“…139). 143 Consistently, the Y2 agonist PYY 3-36 was shown to inhibit diarrhea by reducing intestinal fluid secretion and slowing colonic transit in mice. 140 In smooth muscle cells, the Y2 receptor can activate G-protein Gq and stimulate IPs formation to induce IP 3 -dependent Ca 2+ release and muscle contraction 141 that is related to gastrointestinal transit time and gastric emptying.…”

Peptide YY, neuropeptide Y and corticotrophin‐releasing factor modulate gastrointestinal motility and food intake during acute stress

“…Here NPY, via PVN Y1 receptors, and CRF, acting via PVN CRF 1 receptors, together with CRF released peripherally, via CRF 1 receptors expressed in both the proximal and distal GI tract, are responsible for the central promotile colonic response to stress. However activation of peripheral Y2 receptors, highly expressed in the colon, by NPY (or PYY), or peripheral CRF 2 receptors, which are colocalized with CRF and neuronal nitric oxide synthase in the rat colon, by CRF, opposes this central stimulation and inhibits colonic motility . Interestingly restrained NPY−/− mice produce more fecal pellets, have slowed upper GI motility, and reduced food intake compared to wild type (WT) mice .…”

“…Interestingly restrained NPY−/− mice produce more fecal pellets, have slowed upper GI motility, and reduced food intake compared to wild type (WT) mice . Peptide YY potently activates both the ileal and colonic brakes in man, and exogenous PYY and PYY(3‐36) inhibit colonic transit under normal and stress‐stimulated conditions via peripheral Y2 receptors in mice; however, the functional deficits exhibited by mice lacking endogenous PYY during stress have yet to be established.…”