Peripheral peptide YY inhibits propulsive colonic motor function through Y2 receptor in conscious mice.
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.
Wang
Lixin
L
CURE/Digestive Diseases Research Center, and Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA. lixinw@ucla.edu
Gourcerol
Guillaume
G
Yuan
Pu-Qing
PQ
Wu
S Vincent
SV
Million
Mulugeta
M
Larauche
Muriel
M
Taché
Yvette
Y
D006916:5-Hydroxytryptophan / Q000378:metabolism / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D003243:Consciousness; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010446:Peptide Fragments; D019894:Peptide YY / Q000378:metabolism* / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
D001552:Benzazepines; D009478:Neuropeptide Y; D010277:Parasympathomimetics; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D018723:Bethanechol; D019894:Peptide YY; C061785:peptide YY (3-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D001120:Arginine; D006916:5-Hydroxytryptophan; C403256:BIIE 0246