- Email: [email protected]
Gastrin transcriptionally regulates trefoil family factor 2
T928
to the nuclei of the surface epithelial and neck cells of the mucosal proliferative zone. In cells of the deeper mucosal layer, survivin signal was weaker and more diffused. In the epithelial cells of the ulcer margin survivin signal was significantly increased by two to three fold (p-values <0.005) compared to deeper mucosa. EGFR was also localized to cells of the proliferative zone and cells lining the ulcer margin. Conclusions: I) Survivin is present in normal gastric mucosa, and its expression is induced during ulcer healing 2) Survivin is localized to the nucleus of the surface epithelial cells, and to the proliferative zone cells and regenerating epithelial cells. 3) In the ulcer margin survivin is localized to ceils expressing EGFR, suggesting their local interactions during ulcer healing.
Gastrin Transcriptionally Regulates Trefoil Family Factor 2 Alfred L. Chi, Sconhee l.im, Guanglin Cui, Shigeo Takaishi, John V. Fleming, Chunwei Lee, Timothy C. Wang The trefoil family factor 2, also know as spasmolytic peptide containing a dual-trefoil domain, is secreted by mucous neck cells of stomach and proposed to be the principal cytoprotective tretbil peptide. ]'he antral hormone gastrin was known tot its acid stimulating properties and inducing proliferation of the acid secreting mucosa. The recent TFF2-deficient mice demonstrating a decreased thickness and proliferation rate of the gastric mucosa prompt us investigating whether gastrin is a mediator of TFF2. In gastrin-deficient mice, TFF2 is lound to he siguificant decreased expression in fundus of the stomach, as determined by immunohistochemistry with an antibody specifically recognizing the whole mouse TFF2 protein. Furthermore, TFF2 mRNA expression was rapidly and potently" induced by gastrin in AGS ceils that are stablely introduced the gastrin/CCKB receptor. A series of deletion mutants containing mouse promoter sequence are constructed in a dual-luciferase reporter to map gastrin t~spons~ve elements. Cells co-transfected with prompter constructs and internal control, treated with 10-7M of gastrin for 18 h are subsequently measured the ludterase activities. The results indicate that gastrin-treated cells show much higher hiciferase acti~aty while had little effect on the reporter vector itself. P-46 and P-306, containing 46bp and 306bp of upstream sequence of the transcriptional start site, respectively, have a 38 and 59 fold increase in luciferase activity' over those non-treated AGS cells. The increases in lucilerase activity are largely abolished when 10-6 M of YF476, a chemical antagonist of gastrin/CCKg receptor were added with gastrin, suggesting that increase of TFF2 promoter activity is gastrin-specific mediation through its receptor. These results indicate that multiple gastrin responsive elements are located within these regions. In conclusion, our data suggest that gasmn is manscriptionally regulating TFF2 thus may play an important role in mediating the physiological function of trefoil family factors.
T931
COX-2 But Not Cox-1 Protects Gastric Mucosa Against Ischemia-Reperfusion Injuries Via Down-Regulation of ICAM-1 Expression in Mice Tetsuro Hiratsuka, Seiji Futagami, Atsnshi Tatsuguchi, Kenji Suzuki, Masanori Kusunoki, Yoko Shinji, Kei Shinoki, Katya Gudis, Hitoshi Nishigaki, Ken Wada, Kazumasa Miyake, Taku Tsukui, Choitsu Sakamoto (Background/Aims) Studies have shown that cyclooxygenase-2 (COX-2) induced in various gastrointestinal diseases may be involved in either mucosal de|ense mechanism or repair processes However, the mechanism of its action in the gastric mucosa is not yet determined. On the other hand, various studies have suggested neutrophil activation initiated by its adhesion to endothelial cells as the first step in mucosal injury. Thus, we exanrined whether COX-2 suppresses neutrophil activation through intercellular adhesion molecule-1 (ICAM1) regulation in gastric ischemia-reperfusion (IR) damaged mice.(Methods) lsehemia was induced in mice by clamping the celiac artery {br 30 min, followed by"removal of the damp for 90 min.NS-398 (10mg/kg i.p.), a selective COX-2 inhibitor, or SC-560 (40mg/kg p.o.), a selective COX-1 inhibitor, or rebamipide (100 mg/kg i.p.), a mucoprotectis,e agent known to induce COX-2 in the mucosa, was administered to mice 60 rain before ischemia. Gastric damage was evaluated histologically and by measuring myeloperoxidase (MPO) activity. COX protein expression was evaluated by western blot analysis and ICAM-1 expression in the gastric mucosa was determined by ELISA. To examine whether the effect of NS-398 is related to suppression of endogenous PGs, mice treated v,4th NS-398 received injections of 16,16-dimethyl-PGE2(4ng/kg s.c.) 65 and 2 min before ischemia. (Results) Gastric mucosal injury- was found histologically after IR30 90. MPO activity in the mucosa also increased, but insignificantly. COX-2 expression was induced in the mucosa 90 rain after repertusion, while COX-1 expression remained unaltered. ICAM-1 expression of the gastric mucosa significantly- increased following 1R. NS-398 pretreatment not only aggravated mucosal damage, but also increased MPO activity- in IR mice mucosa. Furthermore, NS-398 pretreatment significantly increased ICAM- 1 expression of the mucosa. Pretreatment with exogenous PGE2 reversed the effect of NS-398. On the other hand, SC-560 pretreatment did not affect mucosal injury, MPO activity or ICAM-1 expression in the mucosa of 1R mice. Rehamipide pretreaturent reduced both COX-2 expression and IR injury,suggesting that rebamipide reduced gastric 1Rinjury via mechanisms independent of COX-2 expression in mice. (Conclusions) PGE2 derived from COX-2 protein induced in the gastric mucosa by 1R might play an important role in the defense mechanism via down-regulating ICAM-1 expression in the gastric mucosa.
T929
Immunoneutralization of Monocyte Chemotactic Protein-1 Inhibited Recurrence of Gastric Ulcer Induced by Tnf-A in Rats Toshio Watanabe, Kazuhide Higuehi, Masaki Hamaguchi, Masatsugu Shiba, Kazunari Tominaga, Yasuhiro Fujiwara, Nobuhide Oshitani, Takayuki Matsumoto, Tetsuo Arakawa Background: We previously demonstrated that tumor necrosis factor (TNF)-c~ induced gastric ulcer recurrence in rats, and that ulcer recurrence was neutrophfl-dependent. In this model of ulcer recm'rence, increases in macrophage infiltration and expression of monocyte chemotactic protein (MCP)-I, the C-C chemokine which mediates chemota~xis of monocytes/ macmphages, primanly occm-, followed by increase in neutrophil infiltration in the late phase of ulcer recurrence, accompanied by up-regulation of macrophage inflammatory protein (MIP)-2tL the C-X-C chemokine whmh promotes migration of neutrophils. Aims: We used an MCP-l neutralizing antibody to examine the roles of MCP-1 in leukocyte infiltration and expression of the C-X-C chemokines including MIP-2ct and cytokine-induced neutrophil chemoattractant (CINC)-2~ during gastric ulcer recurrence. Methods: On day 90 after production of gastric ulcers, endoscopy was done, and rats found to have healed ulcers were used. The rats received an i.p. injection of 1 b~g/kg TNF-~t to induce ulcer recurrence. Some rats were given anti-MCP-1 antibody together with TNF-c~. Scarred mucosa were subjected to measurement of myeloperoxidase activity (a marker of nentrophil infiltration), assay of mRNA levels of MCP-1, MIP-2a and CINC-2ct by real-time RT-PCR, and immunohistochemical staining tot chemokines and monocytes/macrophages. Results: No recurrence was t0und in any group within 24 h. By 48 h, 9 of the 10 healed ulcers in the group given TNF-ct had recrarred. The ulcer recurrence induced by TNF-c~ was significantly inhibited by the administration of anti-MCP-1 antibody; only one of the 6 healed ulcers had recurred in this group. Treatment with TNF-a caused a 7.l-fold increase in mRNA expression of MCP-1 by" 4 h, and a 19.8-fold and 8.8-fold increase in mRNA expression of MIP-2a and CINC-2c~, respectively-, by" 24 h. Administration of anti-MCP-1 antibody inhibited increase in mydoperoxidase activity in scarred mucosa as well as the number of monocytes/macrophages infiltrating scarred mucosa by 24 h, and also inhibited increase in expression of mRNAs tbr MIP-2er and CINC-2cc Chemokines were mainly detected in macrophages in scarred mucosa. Conclusions: MCP-1 plays a crucial role in gastric ulcer recurrence induced by TNF-c~ by stimulating the recruitment of monocytes. Since macrophages are a main source of the chemokines, MCP-1 may regulate neutrophil infiltration via induction of C-X-C chemokine expression, leading to ulcer recurrence.
T932
Stimulation by Capsaicin of Duodenal H C O f Secretion via Afferent Neurons and Vaninoid Receptors in Rats: Comparison with Acid-Induced HCO3 Response Shigem Kagawa, Masako Aoi, Shinichi Kato, Koli Takeuchi Capsaicm shows a variety of actions in the gastrointestinal tract, including duodenal HCO3 secretion, through stimulation of sensory afferent neurons (CSN) and partially depending on endogenous prostaglandins (PG). It is know'n that capsaicin stimulates these afferent neurons through activation of vanilloid receptor type 1 (\~1), yet the role VR1 plays in regulation of the HCO3 secretion has not been much studied. In the present study, we compared the HCO3 secretory response to capsaidn and mucosal acidification in rat duodenums, especially in relation to sensory" aft~rent neurons and VR1. Methods: Male SD rats were used after 18 h fasting. A proximal duodenal loop was perfnsed with saline, and the H C Q secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HC1 The HCOf secretion was stimulated by exposing the loop to capsaicin (0.03~0.3 rag/ ml) or 10 mM HCI for 10 rain. L-NAME was given 1V 3 h before exposure to capsaicin or HC1, while ruthenium red (the VR1 antagonis0 or indomethacin was given IV or SC, respectively, 30 min before these treatment. Results: Luminal application of capsaicin increased the HCO~ secretion in a dose-dependem manner; this effect was totally"attenuated by chemical ablation of CSN as wall as pretreatment with ruthenium ~d, and significantly mitigated by mdomethacin or L-NAME in a L-argmine-sensitive manner. The HCOf secretion was also stimulated by mucosal acidification, and Ibis response was attenuated by' both sensory deafferentation, indomethacin and L-NAME, but not ruthenium red, Mucosal application of capsaicin as well as acid increased PGE2 content in the duodenum, and these effects were both significantly attenuated by indomethacin and L-NAME. Conclusion: These results suggest that both capsaicin and acid cause the CSN-dependent increase m duodenal HCO:? secretion mediated by NO and PG, yet the mode of their action differs m terms of the mtheninm red sensitivity. Although luminal H + plays a modulator,/' role in duodenal HCO3 secretion, it is unlikely that the action results from the interaction of H § with the ruthenium red-sensitive site of VR1.
T930
Expression of Survivin in Normal and Ulcerated Gastric Mucosa : Association with EGFR Expression Shiun-Kwei Chiou, Woo Sung Moon, AndrzeI Tamawski Background: Healing of gastric ulcer is an actire process involving reconstruction of the mucosal detect with proliferating epithelial and com~ective tissue cells. Epidermal growth factor (EGF) stimulation via specific EGF receptors induces cell proliferation and accelerates ulcer healing. Inhibition of apoptusis has also been shown m accelerate healing of gastric lesinns. Survivin, a member of the Inhibitor of Apoptosis Protein (lAP) family, is a 16.5 KD protein implicated in inhibition of apoptosis and cell division. It is expressed in a variety ot cancers, including gastric cancer. However, the expression of sur,'ivin in normal or ulcerated gastric mucc~ has not been investigated, forming the rationale for this stud)'. MethMs: Gastric ulcers were produced in rats by focal serosal application of 100% acetic acid Normal and ulcerated gastric tissues were collected 3, 7, and 14 days after uker induction. Studies: 1) Quantitative histology was performed to determine the expression level as well as localization of survivin in normal and ulcerated gastric mucosa. 2) Survivin expression was also determined by RT-PCR and Western Blot analysis. 3) Expression of EGFR was determined by immunolluorescence staining using specific antibody. Results: RTPCR and Western Blot analysis demonstrated survistn mRNA and protein expression in nomtal and ulcerated gastric mucosa. In normal gastric mucosa, survu~in protein is localized
T933
Role of Prostaglandin EP4 Receptors in Duodenal Bicarbonate Secretion in Rats Masako Aoi, Emi Nakajima, Masato Nakashima, Koji Takeuchi Prostaglandin (PG) plays as a potent biological mediator in diverse physiological fimctions, including duodenal HCO3 secretion. We previously reported that the HCO3 stimulator,/ action of PGE2 in tire duodenum is mediated by' activation of EP3 receptors. At that time,
A-451
AGA Abstracts
to the nuclei of the surface epithelial and neck cells of the mucosal proliferative zone. In cells of the deeper mucosal layer, survivin signal was weaker and more diffused. In the epithelial cells of the ulcer margin survivin signal was significantly increased by two to three fold (p-values <0.005) compared to deeper mucosa. EGFR was also localized to cells of the proliferative zone and cells lining the ulcer margin. Conclusions: I) Survivin is present in normal gastric mucosa, and its expression is induced during ulcer healing 2) Survivin is localized to the nucleus of the surface epithelial cells, and to the proliferative zone cells and regenerating epithelial cells. 3) In the ulcer margin survivin is localized to ceils expressing EGFR, suggesting their local interactions during ulcer healing.
Gastrin Transcriptionally Regulates Trefoil Family Factor 2 Alfred L. Chi, Sconhee l.im, Guanglin Cui, Shigeo Takaishi, John V. Fleming, Chunwei Lee, Timothy C. Wang The trefoil family factor 2, also know as spasmolytic peptide containing a dual-trefoil domain, is secreted by mucous neck cells of stomach and proposed to be the principal cytoprotective tretbil peptide. ]'he antral hormone gastrin was known tot its acid stimulating properties and inducing proliferation of the acid secreting mucosa. The recent TFF2-deficient mice demonstrating a decreased thickness and proliferation rate of the gastric mucosa prompt us investigating whether gastrin is a mediator of TFF2. In gastrin-deficient mice, TFF2 is lound to he siguificant decreased expression in fundus of the stomach, as determined by immunohistochemistry with an antibody specifically recognizing the whole mouse TFF2 protein. Furthermore, TFF2 mRNA expression was rapidly and potently" induced by gastrin in AGS ceils that are stablely introduced the gastrin/CCKB receptor. A series of deletion mutants containing mouse promoter sequence are constructed in a dual-luciferase reporter to map gastrin t~spons~ve elements. Cells co-transfected with prompter constructs and internal control, treated with 10-7M of gastrin for 18 h are subsequently measured the ludterase activities. The results indicate that gastrin-treated cells show much higher hiciferase acti~aty while had little effect on the reporter vector itself. P-46 and P-306, containing 46bp and 306bp of upstream sequence of the transcriptional start site, respectively, have a 38 and 59 fold increase in luciferase activity' over those non-treated AGS cells. The increases in lucilerase activity are largely abolished when 10-6 M of YF476, a chemical antagonist of gastrin/CCKg receptor were added with gastrin, suggesting that increase of TFF2 promoter activity is gastrin-specific mediation through its receptor. These results indicate that multiple gastrin responsive elements are located within these regions. In conclusion, our data suggest that gasmn is manscriptionally regulating TFF2 thus may play an important role in mediating the physiological function of trefoil family factors.
T931
COX-2 But Not Cox-1 Protects Gastric Mucosa Against Ischemia-Reperfusion Injuries Via Down-Regulation of ICAM-1 Expression in Mice Tetsuro Hiratsuka, Seiji Futagami, Atsnshi Tatsuguchi, Kenji Suzuki, Masanori Kusunoki, Yoko Shinji, Kei Shinoki, Katya Gudis, Hitoshi Nishigaki, Ken Wada, Kazumasa Miyake, Taku Tsukui, Choitsu Sakamoto (Background/Aims) Studies have shown that cyclooxygenase-2 (COX-2) induced in various gastrointestinal diseases may be involved in either mucosal de|ense mechanism or repair processes However, the mechanism of its action in the gastric mucosa is not yet determined. On the other hand, various studies have suggested neutrophil activation initiated by its adhesion to endothelial cells as the first step in mucosal injury. Thus, we exanrined whether COX-2 suppresses neutrophil activation through intercellular adhesion molecule-1 (ICAM1) regulation in gastric ischemia-reperfusion (IR) damaged mice.(Methods) lsehemia was induced in mice by clamping the celiac artery {br 30 min, followed by"removal of the damp for 90 min.NS-398 (10mg/kg i.p.), a selective COX-2 inhibitor, or SC-560 (40mg/kg p.o.), a selective COX-1 inhibitor, or rebamipide (100 mg/kg i.p.), a mucoprotectis,e agent known to induce COX-2 in the mucosa, was administered to mice 60 rain before ischemia. Gastric damage was evaluated histologically and by measuring myeloperoxidase (MPO) activity. COX protein expression was evaluated by western blot analysis and ICAM-1 expression in the gastric mucosa was determined by ELISA. To examine whether the effect of NS-398 is related to suppression of endogenous PGs, mice treated v,4th NS-398 received injections of 16,16-dimethyl-PGE2(4ng/kg s.c.) 65 and 2 min before ischemia. (Results) Gastric mucosal injury- was found histologically after IR30 90. MPO activity in the mucosa also increased, but insignificantly. COX-2 expression was induced in the mucosa 90 rain after repertusion, while COX-1 expression remained unaltered. ICAM-1 expression of the gastric mucosa significantly- increased following 1R. NS-398 pretreatment not only aggravated mucosal damage, but also increased MPO activity- in IR mice mucosa. Furthermore, NS-398 pretreatment significantly increased ICAM- 1 expression of the mucosa. Pretreatment with exogenous PGE2 reversed the effect of NS-398. On the other hand, SC-560 pretreatment did not affect mucosal injury, MPO activity or ICAM-1 expression in the mucosa of 1R mice. Rehamipide pretreaturent reduced both COX-2 expression and IR injury,suggesting that rebamipide reduced gastric 1Rinjury via mechanisms independent of COX-2 expression in mice. (Conclusions) PGE2 derived from COX-2 protein induced in the gastric mucosa by 1R might play an important role in the defense mechanism via down-regulating ICAM-1 expression in the gastric mucosa.
T929
Immunoneutralization of Monocyte Chemotactic Protein-1 Inhibited Recurrence of Gastric Ulcer Induced by Tnf-A in Rats Toshio Watanabe, Kazuhide Higuehi, Masaki Hamaguchi, Masatsugu Shiba, Kazunari Tominaga, Yasuhiro Fujiwara, Nobuhide Oshitani, Takayuki Matsumoto, Tetsuo Arakawa Background: We previously demonstrated that tumor necrosis factor (TNF)-c~ induced gastric ulcer recurrence in rats, and that ulcer recurrence was neutrophfl-dependent. In this model of ulcer recm'rence, increases in macrophage infiltration and expression of monocyte chemotactic protein (MCP)-I, the C-C chemokine which mediates chemota~xis of monocytes/ macmphages, primanly occm-, followed by increase in neutrophil infiltration in the late phase of ulcer recurrence, accompanied by up-regulation of macrophage inflammatory protein (MIP)-2tL the C-X-C chemokine whmh promotes migration of neutrophils. Aims: We used an MCP-l neutralizing antibody to examine the roles of MCP-1 in leukocyte infiltration and expression of the C-X-C chemokines including MIP-2ct and cytokine-induced neutrophil chemoattractant (CINC)-2~ during gastric ulcer recurrence. Methods: On day 90 after production of gastric ulcers, endoscopy was done, and rats found to have healed ulcers were used. The rats received an i.p. injection of 1 b~g/kg TNF-~t to induce ulcer recurrence. Some rats were given anti-MCP-1 antibody together with TNF-c~. Scarred mucosa were subjected to measurement of myeloperoxidase activity (a marker of nentrophil infiltration), assay of mRNA levels of MCP-1, MIP-2a and CINC-2ct by real-time RT-PCR, and immunohistochemical staining tot chemokines and monocytes/macrophages. Results: No recurrence was t0und in any group within 24 h. By 48 h, 9 of the 10 healed ulcers in the group given TNF-ct had recrarred. The ulcer recurrence induced by TNF-c~ was significantly inhibited by the administration of anti-MCP-1 antibody; only one of the 6 healed ulcers had recurred in this group. Treatment with TNF-a caused a 7.l-fold increase in mRNA expression of MCP-1 by" 4 h, and a 19.8-fold and 8.8-fold increase in mRNA expression of MIP-2a and CINC-2c~, respectively-, by" 24 h. Administration of anti-MCP-1 antibody inhibited increase in mydoperoxidase activity in scarred mucosa as well as the number of monocytes/macrophages infiltrating scarred mucosa by 24 h, and also inhibited increase in expression of mRNAs tbr MIP-2er and CINC-2cc Chemokines were mainly detected in macrophages in scarred mucosa. Conclusions: MCP-1 plays a crucial role in gastric ulcer recurrence induced by TNF-c~ by stimulating the recruitment of monocytes. Since macrophages are a main source of the chemokines, MCP-1 may regulate neutrophil infiltration via induction of C-X-C chemokine expression, leading to ulcer recurrence.
T932
Stimulation by Capsaicin of Duodenal H C O f Secretion via Afferent Neurons and Vaninoid Receptors in Rats: Comparison with Acid-Induced HCO3 Response Shigem Kagawa, Masako Aoi, Shinichi Kato, Koli Takeuchi Capsaicm shows a variety of actions in the gastrointestinal tract, including duodenal HCO3 secretion, through stimulation of sensory afferent neurons (CSN) and partially depending on endogenous prostaglandins (PG). It is know'n that capsaicin stimulates these afferent neurons through activation of vanilloid receptor type 1 (\~1), yet the role VR1 plays in regulation of the HCO3 secretion has not been much studied. In the present study, we compared the HCO3 secretory response to capsaidn and mucosal acidification in rat duodenums, especially in relation to sensory" aft~rent neurons and VR1. Methods: Male SD rats were used after 18 h fasting. A proximal duodenal loop was perfnsed with saline, and the H C Q secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HC1 The HCOf secretion was stimulated by exposing the loop to capsaicin (0.03~0.3 rag/ ml) or 10 mM HCI for 10 rain. L-NAME was given 1V 3 h before exposure to capsaicin or HC1, while ruthenium red (the VR1 antagonis0 or indomethacin was given IV or SC, respectively, 30 min before these treatment. Results: Luminal application of capsaicin increased the HCO~ secretion in a dose-dependem manner; this effect was totally"attenuated by chemical ablation of CSN as wall as pretreatment with ruthenium ~d, and significantly mitigated by mdomethacin or L-NAME in a L-argmine-sensitive manner. The HCOf secretion was also stimulated by mucosal acidification, and Ibis response was attenuated by' both sensory deafferentation, indomethacin and L-NAME, but not ruthenium red, Mucosal application of capsaicin as well as acid increased PGE2 content in the duodenum, and these effects were both significantly attenuated by indomethacin and L-NAME. Conclusion: These results suggest that both capsaicin and acid cause the CSN-dependent increase m duodenal HCO:? secretion mediated by NO and PG, yet the mode of their action differs m terms of the mtheninm red sensitivity. Although luminal H + plays a modulator,/' role in duodenal HCO3 secretion, it is unlikely that the action results from the interaction of H § with the ruthenium red-sensitive site of VR1.
T930
Expression of Survivin in Normal and Ulcerated Gastric Mucosa : Association with EGFR Expression Shiun-Kwei Chiou, Woo Sung Moon, AndrzeI Tamawski Background: Healing of gastric ulcer is an actire process involving reconstruction of the mucosal detect with proliferating epithelial and com~ective tissue cells. Epidermal growth factor (EGF) stimulation via specific EGF receptors induces cell proliferation and accelerates ulcer healing. Inhibition of apoptusis has also been shown m accelerate healing of gastric lesinns. Survivin, a member of the Inhibitor of Apoptosis Protein (lAP) family, is a 16.5 KD protein implicated in inhibition of apoptosis and cell division. It is expressed in a variety ot cancers, including gastric cancer. However, the expression of sur,'ivin in normal or ulcerated gastric mucc~ has not been investigated, forming the rationale for this stud)'. MethMs: Gastric ulcers were produced in rats by focal serosal application of 100% acetic acid Normal and ulcerated gastric tissues were collected 3, 7, and 14 days after uker induction. Studies: 1) Quantitative histology was performed to determine the expression level as well as localization of survivin in normal and ulcerated gastric mucosa. 2) Survivin expression was also determined by RT-PCR and Western Blot analysis. 3) Expression of EGFR was determined by immunolluorescence staining using specific antibody. Results: RTPCR and Western Blot analysis demonstrated survistn mRNA and protein expression in nomtal and ulcerated gastric mucosa. In normal gastric mucosa, survu~in protein is localized
T933
Role of Prostaglandin EP4 Receptors in Duodenal Bicarbonate Secretion in Rats Masako Aoi, Emi Nakajima, Masato Nakashima, Koji Takeuchi Prostaglandin (PG) plays as a potent biological mediator in diverse physiological fimctions, including duodenal HCO3 secretion. We previously reported that the HCO3 stimulator,/ action of PGE2 in tire duodenum is mediated by' activation of EP3 receptors. At that time,
A-451
AGA Abstracts