title: Preconditioning stress prevents cold restraint stress-induced gastric lesions in rats: roles of COX-1, COX-2, and PLA2.
abstract: We investigated the protective effect of mild stress on gastric lesions induced by cold-restraint stress, especially concerning prostaglandins (PGs)/cyclo-oxygenase (COX) isozymes. Rats were exposed to severe stress (cold-restraint stress at 10 degrees C for 6 hr) or mild stress (cold-restraint stress at 10 degrees C for 30 min and kept at room temperature for 60 min) followed by severe stress. Severe stress induced gastric lesions, with a concomitant decrease in body temperature (BT). The ulcerogenic response was inhibited by atropine but worsened by indomethacin and SC-560 but not rofecoxib, although none of these agents had any effect on the change in BT. Mild stress suppressed the gastric ulceration and the decrease in BT induced by severe stress, and these effects were reversed by both COX-1 and COX-2 inhibitors. The expression of COX-2 in the stomach was up-regulated from 4 hr after severe stress and this response was slightly expedited by mild stress. COX-2 was also expressed in the hypothalamus under normal and stressed conditions. Quinacrine (phospholipase A(2) inhibitor) attenuated the protective effect of mild stress on the ulceration and decrease in BT caused by severe stress. TA-0910 (TRH analogue) at a low dose also prevented the gastric ulceration and the decrease in BT induced by severe stress. These results suggest that mild stress protects against cold-restraint stress-induced gastric ulceration, and the effect is peripherally and centrally mediated by PGs derived from both COX-1 and COX-2 through the activation of phospholipase A(2). TRH may also be involved in the protective effect of mild stress, probably through regulation of the thermogenic system.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatazawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahira
authors.forename: Nahoko
authors.initials: N
authors.lastname: Izumi
authors.forename: Ludmila
authors.initials: L
authors.lastname: Filaretova
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001831:Body Temperature; D003080:Cold Temperature / Q000009:adverse effects; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000209:etiology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone