PMID- 11356923
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 297
IP  - 3
DP  - 2001 Jun
TI  - Supraspinal delta- and mu-opioid receptors mediate gastric mucosal protection in 
      the rat.
PG  - 1010-5
AB  - This study evaluated the contribution of supraspinal opioid receptors to gastric 
      mucosal protection in the rat. Intracerebroventricular (i.c.v.) and 
      intracisternal (i.c.) injections of selective delta- 
      [[D-Ala(2),D-Leu(5)]-enkephalin (DADLE), [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE), 
      deltorphin II], selective mu- [[D-Ala(2),Phe(4),Gly(5)-ol]-enkephalin (DAGO)] 
      opioid receptor agonists and beta-endorphin (ligand of both receptor types) 
      produced a dose-dependent inhibition of acidified ethanol-induced gastric mucosal 
      damage. The ED(50) values for beta-endorphin, DAGO, DADLE, deltorphin II, and 
      DPDPE were 3.5, 6.8, 75, 120, and 1100 pmol/rat, respectively, following i.c.v. 
      and 0.8, 9.0, 45, 0.25, and 7 pmol/rat following i.c. injection. The 
      gastroprotective effect of DADLE, deltorphin II, and DPDPE, but not that of DAGO, 
      was inhibited by naltrindole, the selective delta-receptor antagonist. Since the 
      delta(2)-receptor agonist deltorphin II was more potent than the 
      delta(1)-receptor agonist DPDPE, the dominant role of central delta(2)-receptors 
      in gastroprotection might be raised. The site of action for delta-receptor 
      agonists is likely to be the brain stem since the peptides were more potent 
      following i.c. than following i.c.v. administration. The gastroprotective effect 
      was reduced following acute bilateral cervical vagotomy. Moreover, both the 
      nitric-oxide synthase inhibitor N(G)-nitro-L-arginine (3 mg/kg i.v.) and the 
      prostaglandin synthesis inhibitor indomethacin (20 mg/kg p.o.) decreased the 
      protective effect of opioid peptides. The results indicate that 1) activation of 
      supraspinal delta- and mu-opioid receptors induces gastric mucosal protection, 2) 
      integrity of vagal nerve is necessary for the gastroprotective action of opioids, 
      and 3) mucosal nitric oxide and prostaglandins may be involved in the 
      opioid-induced gastroprotection.
FAU - Gyires, K
AU  - Gyires K
AD  - Semmelweis University, Faculty of Medicine, Department of Pharmacology and 
      Pharmacotherapy, Budapest, Hungary. Gyirkla@NET.SOTE.HU
FAU - Ronai, A Z
AU  - Ronai AZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Enkephalins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (Receptors, Opioid, mu)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 122752-16-3 (deltorphin II, Ala(2)-)
RN  - 3K9958V90M (Ethanol)
RN  - 60617-12-1 (beta-Endorphin)
RN  - 63631-40-3 (Enkephalin, Leucine-2-Alanine)
RN  - 88373-73-3 (Enkephalin, D-Penicillamine (2,5)-)
RN  - QTT17582CB (Hydrochloric Acid)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Capsaicin/administration & dosage
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Routes
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/administration & dosage
MH  - Enkephalin, D-Penicillamine (2,5)-/administration & dosage
MH  - Enkephalin, Leucine-2-Alanine/administration & dosage
MH  - Enkephalins/administration & dosage
MH  - Enzyme Inhibitors/administration & dosage
MH  - Ethanol
MH  - Gastric Mucosa/drug effects/*physiology
MH  - Hydrochloric Acid
MH  - Male
MH  - Narcotic Antagonists/administration & dosage
MH  - Oligopeptides/administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, delta/agonists/antagonists & inhibitors/*metabolism
MH  - Receptors, Opioid, mu/agonists/*metabolism
MH  - Stomach Ulcer/chemically induced/*prevention & control
MH  - Vagotomy
MH  - beta-Endorphin/administration & dosage
EDAT- 2001/05/18 10:00
MHDA- 2001/06/23 10:01
CRDT- 2001/05/18 10:00
PHST- 2001/05/18 10:00 [pubmed]
PHST- 2001/06/23 10:01 [medline]
PHST- 2001/05/18 10:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2001 Jun;297(3):1010-5.