Acute uterine irritation provokes colonic motility via transient receptor potential A(1)-dependent spinal NR2B phosphorylation in rats.
BACKGROUND
Patients with inflammatory gynecological/obstetrical problems often complain of irritable bowel syndrome. The authors examined whether acute uterus irritation reflexively provokes colonic motility in rat preparations.


METHODS
A modified colon manometry and striated abdominal muscle electromyogram activity in response to mustard oil (MO) instillation into the uterine horn were continuously recorded in anesthetized rats. The lumbosacral (L6-S1) dorsal horn was dissected to assess the level and the cellular location of phosphorylated NR2B subunit using Western blotting and immunofluorescence analysis, respectively. Finally, the uterine transient receptor potential A1 or spinal NR2B subunit was pharmacologically blocked to elucidate its roles.


RESULTS
MO (0.1%, 0.2 ml) injected into the lower uterine horn dramatically provoked colonic hypermotility characterized by rhythmic colonic contractions (about 3-4 contractions per 10 min, n = 7) accompanied by synchronized electromyogram firing in the abdominal muscle (about 4-5 folds of control, n = 7). In addition to provoking colonic hypermotility, MO administration also up-regulated phosphorylated (about 2-3 folds of control, n = 7), but not total, NR2B expression in the dorsal horn neurons. Both intrathecal Ro 25-6981 (a selective NR2B subunit antagonist; 10 μM, 10 μl) and intrauterine HC-030031 (a selective transient receptor potential A1 receptor antagonist; 30 mg/kg, 0.2 ml) injected before the MO instillation attenuated the MO-induced colonic hypermotility and spinal NR2B phosphorylation.


CONCLUSIONS
The comorbidity of gynecological/obstetrical and gastrointestinal problems is not coincidental but rather causal in nature, and clinicians should investigate for gynecological/urological diseases in the setting of bowel problems with no known pathological etiology.
From the Department of Medicine (H.-Y.P, Y.-P.C.), Mackay Medical College, New Taipei, Taiwan; Division of Thoracic Surgery, Department of Health (C.-M.Y.), Taichung Hospital, Executive Yuan, Taichung, Taiwan; Department of Anesthesiology (J.-K.C.), Mackay Memorial Hospital, New Taipei, Taiwan; School of Medicine (T.R.), Fu-Jen Catholic University, New Taipei, Taiwan; Department of Obstetrics and Gynecology (G.-D.C.), Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan; Department of Physiology, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, and Department of Medicine, Mackay Medical College (M.-C.H.); Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan, and Department of Medicine, Mackay Medical College (C.-Y.L.); and Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, and Department of Biotechnology, Asia University, Taichung, Taiwan, and Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University (T.-B.L.), Taipei, Taiwan. Drs. Peng and Lin contributed equally to this work.
Hsien-Yu
HY
Peng
Chou-Ming
CM
Yeh
Jen-Kun
JK
Cheng
Yat-Pang
YP
Chau
Ting
T
Ruan
Gin-Den
GD
Chen
Ming-Chun
MC
Hsieh
Cheng-Yuan
CY
Lai
Tzer-Bin
TB
Lin
D000083:Acetanilides / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000378:metabolism; D007509:Irritants; D009149:Mustard Plant; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D010938:Plant Oils; D020671:Posterior Horn Cells / Q000187:drug effects; D011312:Pressure; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D014591:Uterine Diseases / Q000139:chemically induced / Q000503:physiopathology*; D014599:Uterus / Q000502:physiology*
C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D001798:Blood Proteins; D018691:Excitatory Amino Acid Antagonists; D054439:Ghrelin; D007509:Irritants; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D010938:Plant Oils; D011687:Purines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D019342:Acetic Acid; C027793:mustard oil