Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.
OBJECTIVE
Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients.


METHODS
Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg).


RESULTS
ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH.


CONCLUSIONS
Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.
Sagami
Y
Y
Department of Psychosomatic Medicine, Tohoku University School of Medicine, Sendai, Japan.
Shimada
Y
Y
Tayama
J
J
Nomura
T
T
Satake
M
M
Endo
Y
Y
Shoji
T
T
Karahashi
K
K
Hongo
M
M
Fukudo
S
S
D015746:Abdominal Pain / Q000503:physiopathology / Q000523:psychology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000339:Affect / Q000187:drug effects; D001007:Anxiety / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D003109:Colonic Diseases, Functional / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009129:Muscle Tonus; D011312:Pressure; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D012677:Sensation / Q000187:drug effects; D012684:Sensory Thresholds; D013312:Stress, Physiological / Q000503:physiopathology
D005765:Gastrointestinal Agents; D018019:Receptors, Corticotropin-Releasing Hormone; C069206:alpha helical corticotropin-releasing hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone