Role of neurokinin 3 receptors on responses to colorectal distention in the rat: electrophysiological and behavioral studies.
OBJECTIVE
Tachykinins contribute to the control of gastrointestinal motility and modulation of somatic and visceral pain. The role of neurokinin (NK) B and NK3 receptors in visceral pain and gastrointestinal disorders has not been determined.


METHODS
Using electromyographic recordings of both abdominal and colonic muscle and electrophysiological recordings of pelvic nerve afferent fibers, we studied drug effects on responses to colorectal distention.


RESULTS
In awake rats, intraperitoneal administration of the NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agonist senktide increased, both the rectocolonic inhibitory reflex and abdominal contractions produced by colorectal distention. In contrast, intracerebroventricular administration of SR 142,801 increased the number of abdominal contractions without affecting the rectocolonic inhibitory reflex produced by colorectal distention. In a similar manner, intracerebroventricular injection of senktide diminished the number of abdominal contractions. In electrophysiological experiments, SR 142,801 decreased responses of pelvic nerve afferent fibers to colorectal distention. Responses of pelvic nerve fibers to urinary bladder distention, however, were unaffected by SR 142,801.


CONCLUSIONS
These results suggest that peripheral NK3 receptors are involved in the mediation of both visceral nociception and gastrointestinal disorders. Also, central NK3 receptors seem to play a role in the modulation of visceral nociception.
Julia
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Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa, USA.
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Buéno
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Gebhart
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D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012007:Rectum / Q000187:drug effects / Q000502:physiology*; D012684:Sensory Thresholds; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D017833:Visceral Afferents / Q000187:drug effects / Q000502:physiology
D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; C091554:SR 142801