Role of capsaicin sensitive nerves in epidermal growth factor effects on gastric mucosal injury and blood flow

Background—Epidermal growth factor (EGF) and capsaicin protect against experimental gastric mucosal injury. Capsaicin exerts its gastroprotective effect by stimulating afferent neurones leading to release of calcitonin gene related peptide (CGRP) which causes gastric hyperaemia. EGF also causes gastric hyperaemia but whether it acts via capsaicin sensitive neurones is unknown.Aims—To assess the influence of: (1) capsaicin desensitisation on EGF effects on gastric mucosal injury and gastric mucosal blood flow; and (2) close arterial infusion of hCGRP8–37, a CGRP antagonist, on EGF effects on gastric mucosal blood flow.Methods—The absolute ethanol induced gastric mucosal injury model in the rat was used. Gastric mucosal damage was assessed by planimetry and light microscopy. Gastric mucosal blood flow was measured by laser Doppler flowmetry in a gastric chamber preparation.Results—Capsaicin desensitisation abolished the gastroprotective and gastric hyperaemic effects of EGF. Close arterial infusion of hCGRP8–37 antagonised the hyperaemic effect of both capsaicin and EGF.Conclusion—Results show that EGF may exert its gastroprotective and gastric hyperaemic effects via capsaicin sensitive afferent neurones.

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Preventive Effects of Rebamipide on NSAID-Induced Gastric Mucosal Injury and Reduction of Gastric Mucosal Blood Flow in Healthy Volunteers

Digestive Diseases and Sciences ◽

10.1007/s10620-006-9367-y ◽

2007 ◽

Vol 52 (8) ◽

pp. 1776-1782 ◽

Cited By ~ 40

Author(s):

Hyung-Keun Kim ◽

Jin-Il Kim ◽

Jae-Kwang Kim ◽

Joon-Yeol Han ◽

Soo-Heon Park ◽

...

Keyword(s):

Blood Flow ◽

Healthy Volunteers ◽

Mucosal Blood Flow ◽

Gastric Mucosal Blood Flow ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Preventive Effects

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Role of Epidermal Growth Factor in Protection and Repair of Gastric Mucosal Injury

Journal of Clinical Gastroenterology ◽

10.1097/00004836-199112001-00017 ◽

1991 ◽

Vol 13 ◽

pp. S103-S108 ◽

Cited By ~ 6

Author(s):

Kiwamu Okita ◽

Mikio Karita ◽

Noriko Nakanishi ◽

Tadayoshi Takemoto

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Epidermal Growth

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Monoamine oxidase B inhibition reduces gastric mucosal blood flow, basal acid secretion, and cold water restraint-induced gastric mucosal injury in rats

Digestive Diseases and Sciences ◽

10.1007/bf01537224 ◽

1990 ◽

Vol 35 (1) ◽

pp. 61-65 ◽

Cited By ~ 5

Author(s):

Lianping Xing ◽

John Washington ◽

John Seaton ◽

Gordon Kauffman

Keyword(s):

Blood Flow ◽

Monoamine Oxidase ◽

Acid Secretion ◽

Cold Water ◽

Mucosal Blood Flow ◽

Gastric Mucosal Blood Flow ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Monoamine Oxidase B ◽

Basal Acid

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Transforming Growth Factor Alpha and Epidermal Growth Factor in Protection and Healing of Gastric Mucosal Injury

Scandinavian Journal of Gastroenterology ◽

10.3109/00365529209000134 ◽

1992 ◽

Vol 27 (8) ◽

pp. 649-655 ◽

Cited By ~ 90

Author(s):

S. J. Konturek ◽

T. Brzozowski ◽

J. Majka ◽

A. Dembinski ◽

A. Slomiany ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Transforming Growth Factor ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Transforming Growth Factor Alpha ◽

Epidermal Growth ◽

Factor Alpha

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Epidermal growth factor increases basal mucosal blood flow in the rat colon, a prostaglandin dependent effect

European Journal of Gastroenterology & Hepatology ◽

10.1097/00042737-199911000-00021 ◽

1999 ◽

Vol 11 (11) ◽

pp. 1305-1310 ◽

Cited By ~ 2

Author(s):

Peter Hoffmann ◽

Viktor E. Eysselein ◽

Jörg M. Zeeh ◽

Frank Procaccino ◽

John Kao ◽

...

Keyword(s):

Blood Flow ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Mucosal Blood Flow ◽

Rat Colon ◽

Dependent Effect ◽

Epidermal Growth

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ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.2.g246 ◽

1998 ◽

Vol 274 (2) ◽

pp. G246-G252 ◽

Cited By ~ 8

Author(s):

Z. Morise ◽

S. Komatsu ◽

J. W. Fuseler ◽

D. N. Granger ◽

M. Perry ◽

...

Keyword(s):

Endothelial Cell ◽

Critical Role ◽

Mucosal Blood Flow ◽

Gastric Mucosal Blood Flow ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Intercellular Adhesion Molecule ◽

Sprague Dawley ◽

Intercellular Adhesion Molecule 1 ◽

Mucosal Permeability

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

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Effect of sialoadenectomy on ethanol-induced gastric mucosal damage in the rat: role of neutrophils

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-032 ◽

1990 ◽

Vol 68 (2) ◽

pp. 207-210 ◽

Cited By ~ 11

Author(s):

B. L. Tepperman ◽

B. D. Soper

Keyword(s):

Growth Factor ◽

Gastric Mucosa ◽

Epidermal Growth Factor ◽

Salivary Glands ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Mucosal Inflammation ◽

Prostaglandin E ◽

Epidermal Growth ◽

Extent Of Damage

We have observed that removal of the salivary glands is associated with an increase in the susceptibility to gastric mucosal damage in the rat. In the present study, we have examined the effect of sialoadenectomy on ethanol-induced mucosal hemorrhagic damage and myeloperoxidase (MPO) activity. Hemorrhagic damage and MPO activity in response to intragastric 50% w/v ethanol were greater in sialoadenectomized rats when compared with sham-operated animals. Pretreatment with 16,16-dimethylprostaglandin E2 (0.3 μg/kg s.c.) reduced damage and MPO activity in both sialoadenectomized and sham control rats receiving 50% ethanol. The reduction in these parameters was greater in control than in sialoadenectomized rats. Pretreatment with epidermal growth factor (5 μg/kg s.c.) significantly reduced MPO activity but did not significantly affect the extent of damage. These data suggest that sialoadenectomy is associated with an increase in mucosal inflammation in animals given ethanol. However, in some situations tissue inflammation (as indicated by MPO activity) was reduced, while the proportion of gastric mucosa exhibiting hemorrhagic damage was not changed.Key words: salivary glands, gastric mucosa, neutrophils, prostaglandin E2, epidermal growth factor.

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Gastroprotective and vasodilatory effects of epidermal growth factor: the role of sensory afferent neurons

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.5.g897 ◽

2001 ◽

Vol 280 (5) ◽

pp. G897-G903 ◽

Cited By ~ 9

Author(s):

Yoji Matsumoto ◽

Kohki Kanamoto ◽

Keishi Kawakubo ◽

Hitoshi Aomi ◽

Takayuki Matsumoto ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Mucosal Injury ◽

Protective Role ◽

Sensory Nerves ◽

Afferent Neurons ◽

Gastric Mucosal Lesions ◽

Calcitonin Gene ◽

Epidermal Growth

Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and gastroprotective effects via capsaicin-sensitive afferent neurons, including the release of calcitonin gene-related peptide (CGRP). We examined the protective and vasodilatory effects of EGF on the gastric mucosa and its interaction with sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric EGF (10 or 30 μg) significantly reduced gastric mucosal lesions induced by intragastric 60% ethanol (50.6% by 10 μg EGF and 70.0% by 30 μg EGF). The protective effect of EGF was significantly inhibited by pretreatment with capsaicin desensitization, human CGRP1 antagonist hCGRP-(8–37), or N ω-nitro-l-arginine methyl ester (l-NAME). Intravital microscopy showed that topically applied EGF (10–1,000 μg/ml) dilated the gastric mucosal arterioles dose dependently and that this vasodilatory effect was significantly inhibited by equivalent pretreatments. These findings suggest that EGF plays a protective role against ethanol-induced gastric mucosal injury, possibly by dilating the gastric mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO mechanisms.

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