Functional significance of a newly discovered neuropeptide, orphanin FQ, in rat gastrointestinal motility.
OBJECTIVE
Orphanin FQ (OFQ) is a recently discovered neuropeptide that structurally resembles an opioid peptide. However, the functional role of OFQ in rat gastrointestinal tract remains unknown.


METHODS
We investigated the effects of OFQ on contractions of muscle strips obtained from different regions of the gastrointestinal tract. Immunohistochemical studies were performed on rat colonic tissue using OFQ antibody.


RESULTS
OFQ (10(-9) to 10(-7) mol/L) caused significant contractions in the rat colon but not in the stomach or small intestine. Tetrodotoxin, veratridine, and long-term serosal application of benzalkonium chloride completely abolished OFQ-induced colonic contractions without affecting myogenic contractions in response to carbachol. OFQ-induced contractions were not affected by naloxone, atropine, phentolamine, propranolol, methysergide, substance P antagonist, vasoactive intestinal polypeptide antagonist, apamin, and NG-nitro-L-arginine methyl ester. OFQ (10(-9) to 10(-7) mol/L) significantly reduced muscle contractions and 3H-acetylcholine release in response to electrical field stimulation in both the stomach and small intestine but not in the colon. OFQ-immunopositive neuronal fibers were found in the colonic myenteric plexus.


CONCLUSIONS
These studies indicate that the mechanisms and sites of action of OFQ are region specific. OFQ inhibits cholinergic transmission in the stomach and small intestine, whereas OFQ stimulates colonic contraction possibly by inhibiting an inhibitory neural pathway within the myenteric plexus.
Yazdani
A
A
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0362, USA.
Takahashi
T
T
Bagnol
D
D
Watson
S J
SJ
Owyang
C
C
D000109:Acetylcholine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D000097629:Nociceptin
D000109:Acetylcholine; D018847:Opioid Peptides; D000097629:Nociceptin