Nitric oxide synthase inhibition negates bombesin-induced gastroprotection

Antonio A. Castañeda, Yong S. Kim, Lily K. Chang, Yan Cui, David W Mercer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background. Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. Methods. Rats were given subcutaneous saline or bombesin (10-100 μg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm2). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. Results. Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) L-arginine (300 mg/kg), but not D-arginine, abolished the effects of L-NAME. Conclusions. Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

Original languageEnglish (US)
Pages (from-to)422-428
Number of pages7
JournalSurgery
Volume128
Issue number3
DOIs
StatePublished - Jan 1 2000

Fingerprint

Bombesin
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
Stomach
Nitric Oxide Synthase Type III
Gastrins
Nitric Oxide Synthase Type II
Arginine
Nitric Oxide
Protein Isoforms
Ethanol
Hydrochloric Acid
Hyperemia
Wounds and Injuries
Lasers
Western Blotting
Enzymes

ASJC Scopus subject areas

  • Surgery

Cite this

Nitric oxide synthase inhibition negates bombesin-induced gastroprotection. / Castañeda, Antonio A.; Kim, Yong S.; Chang, Lily K.; Cui, Yan; Mercer, David W.

In: Surgery, Vol. 128, No. 3, 01.01.2000, p. 422-428.

Research output: Contribution to journalArticle

Castañeda, Antonio A. ; Kim, Yong S. ; Chang, Lily K. ; Cui, Yan ; Mercer, David W. / Nitric oxide synthase inhibition negates bombesin-induced gastroprotection. In: Surgery. 2000 ; Vol. 128, No. 3. pp. 422-428.
@article{37c46c75f4e048a6997734d9614e2d8c,
title = "Nitric oxide synthase inhibition negates bombesin-induced gastroprotection",
abstract = "Background. Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. Methods. Rats were given subcutaneous saline or bombesin (10-100 μg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50{\%} ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm2). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. Results. Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) L-arginine (300 mg/kg), but not D-arginine, abolished the effects of L-NAME. Conclusions. Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.",
author = "Casta{\~n}eda, {Antonio A.} and Kim, {Yong S.} and Chang, {Lily K.} and Yan Cui and Mercer, {David W}",
year = "2000",
month = "1",
day = "1",
doi = "10.1067/msy.2000.107982",
language = "English (US)",
volume = "128",
pages = "422--428",
journal = "Surgery (United States)",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Nitric oxide synthase inhibition negates bombesin-induced gastroprotection

AU - Castañeda, Antonio A.

AU - Kim, Yong S.

AU - Chang, Lily K.

AU - Cui, Yan

AU - Mercer, David W

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background. Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. Methods. Rats were given subcutaneous saline or bombesin (10-100 μg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm2). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. Results. Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) L-arginine (300 mg/kg), but not D-arginine, abolished the effects of L-NAME. Conclusions. Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

AB - Background. Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. Methods. Rats were given subcutaneous saline or bombesin (10-100 μg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm2). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. Results. Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) L-arginine (300 mg/kg), but not D-arginine, abolished the effects of L-NAME. Conclusions. Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

UR - http://www.scopus.com/inward/record.url?scp=0033811847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033811847&partnerID=8YFLogxK

U2 - 10.1067/msy.2000.107982

DO - 10.1067/msy.2000.107982

M3 - Article

VL - 128

SP - 422

EP - 428

JO - Surgery (United States)

JF - Surgery (United States)

SN - 0039-6060

IS - 3

ER -