A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.
We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress.
Division of Gastroenterology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.
I
I
Castagliuolo
S E
SE
Leeman
E
E
Bartolak-Suki
S
S
Nikulasson
B
B
Qiu
R E
RE
Carraway
C
C
Pothoulakis
D000818:Animals; D053818:Chymases; D003106:Colon / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism; D005772:Gastrointestinal Transit; D009077:Mucins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors* / Q000235:genetics; D012149:Restraint, Physical; D012697:Serine Endopeptidases / Q000378:metabolism
D009077:Mucins; D011720:Pyrazoles; D011804:Quinolines; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C079087:SR 48692; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D015232:Dinoprostone