Peripheral and central administration of exogenous urocortin 1 disrupts the fasted motility pattern of the small intestine in rats via the corticotrophin releasing factor receptor 2 and a cholinergic mechanism.
OBJECTIVE
The action of the corticotrophin releasing factor (CRF) receptor on the small intestinal motility has been rarely investigated. The present study aimed to determine the effects of urocortin 1 on small intestinal motility in rats and the CRF receptor subtypes and autonomic pathways mediating the effects.


METHODS
Fasted or fed rats were used to investigate the effect of intravenous or intracerebroventricular urocortin 1 on duodenum and jejunum motility. NBI-27914 and astressin(2)-B (CRF receptor 1 and 2 antagonists, respectively), atropine (an M-receptor antagonist), phentolamine (an alpha-receptor antagonist), propranolol (a beta-receptor antagonist) and N(omega)-Nitro-L-arginine (a nitric oxide synthase [NOS] inhibitor) were applied to determine the involved CRF receptor subtypes and autonomic pathways.


RESULTS
In fasted rats, intravenous or intracerebroventricular injection of urocortin 1 disrupted duodenal and jejunal migrating myoelectric complex pattern, leading to an irregular spiking activity similar to the fed motility pattern. When urocortin 1 was given in the fed state, the fed motility pattern remained unchanged. In addition, urocortin 1 also inhibited small intestinal transit function. Astressin(2)-B injected intraperitoneally or intracerebroventricularly blocked urocortin 1-induced change, while NBI-27914 had no effect. The disruption of migrating myoelectric complex induced by urocortin 1 was abolished by atropine, but not affected by phentolamine, propranolol and N(omega)-Nitro-L-arginine.


CONCLUSIONS
Intravenous or intracerebroventricular injection of urocortin 1 acts, respectively, on peripheral and central CRF receptor 2 to disrupt the intestinal migrating myoelectric complex through an M-receptor-dependent mechanism, and such change has an inhibitory effect as proved by measuring the small intestinal transit function.
Yin
Yan
Y
Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Dong
Lei
L
Yin
Dong
D
D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007583:Jejunum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D016065:Myoelectric Complex, Migrating; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D019518:Postprandial Period; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054832:Urocortins / Q000008:administration & dosage* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; C101531:CRF receptor type 2; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C528574:astressin-2B; D019335:Nitroarginine; D001285:Atropine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D010646:Phentolamine