Increased 5-hydroxytryptamine mediates post-inflammatory visceral hypersensitivity via the 5-hydroxytryptamine 3 receptor in rats.
Visceral hypersensitivity often develops after intestinal inflammation, but the pathogenic mechanism has not been clearly elucidated. We investigated whether this post-inflammatory visceral hypersensitivity is mediated by 5-hydroxytryptamine through activation of the 5-hydroxytryptamine 3 receptor. In male Sprague-Dawley rats recovered from acetic acid-induced colitis, we monitored visceral nociceptive response by scoring the abdominal withdrawal reflex and simultaneously measuring the changes in arterial pulse rate. Seven days after induction of colitis, 52% of the rats showed an increased abdominal withdrawal reflex score and arterial pulse rate changes to colorectal distension, indicating that they had post-inflammatory visceral hypersensitivity. The 5-hydroxytryptamine 3 receptor antagonists, alosetron (20 mg/kg, p.o.) and granisetron (10 microg/kg, s.c.), inhibited post-inflammatory visceral hypersensitivity. Administration of a 5-hydroxytryptamine precursor, 5-hydroxytryptophan; 10 mg/kg, s.c.), induced visceral hypersensitivity in naïve rats, which was antagonized by granisetron. Increase in 5-hydroxytryptamine immunoreactive cells in colonic mucosal layer was found both in the rats with post-inflammatory visceral hypersensitivity and in the 5-hydroxytryptophan-treated rats. These results suggest that increased 5-hydroxytryptamine in colonic mucosa mediates post-inflammatory visceral hypersensitivity through activation of the 5-hydroxytryptamine 3 receptor.
Choi
Yun-Dong
YD
Department of Physiology, Seoul National University, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Sung
Tae-Sik
TS
Kim
Hyun-Ju
HJ
La
Jun-Ho
JH
Kim
Tae-Wan
TW
Yang
Il-Suk
IS
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017829:Granisetron / Q000494:pharmacology; D006967:Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists
D006916:5-Hydroxytryptophan; D019342:Acetic Acid; D002243:Carbolines; D017829:Granisetron; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D058831:Serotonin 5-HT3 Receptor Antagonists; C090840:alosetron