Abstract
The gastroprotective effect of opioid peptides, prostaglandin E2 and capsaicin against acidified ethanol-induced gastric mucosal damage in young mature rats of different (6–8 and 14–16 weeks) ages has been investigated. It was found that gastric mucosal damage was more severe in 14–16 weeks old rats. The gastroprotective effect of opioid peptides - [D-Ala2, D-Leu5]-enkephalin (DADLE), deltorphin II, [D-Ala2, Phe4, Gly5 -ol]-enkephalin (DAGO) and β-endorphin - given either intracerebroventricularly (0.6, 3.3., 0.2, and 0.01 nmol/rat, respectively) or subcutaneously (825 and 960 nmol/kg, respectively) was highly reduced in 14–16 weeks old rats. The mucosal protective action of orally administered capsaicin (1600–3200 nmol/kg) and PGE2 (280–560 nmol/kg) was also diminished in 14–16 weeks old animals. Both ACTH and corticosterone plasma levels were significantly higher in 14–16 weeks old rats. These results suggest that the gastric mucosal susceptibility to ethanol and the gastroprotective effect of opioid peptides, capsaicin and PGE2 are age-related.
Similar content being viewed by others
REFERENCES
Bonnevie O: The incidence of gastric ulcer in Copenhagen country. Scand J Gastroneterol 10:231–239, 1975
Kurata JH, Honda GD, Frankl H: The incidence of duodenal and gastric ulcers in a large health maintenance organization. Am J Public Health 75:625–629, 1985
Gronbech JE, Lacy ER: Role of gastric blood flow in impaired defense and repair of aged rat stomach. Am J Physiol 269:G737–G744, 1995
Lee M, Feldman M: Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats. Gastroenterology 107:1746–1750, 1994
Miyake H, Inaba N, Kato S, Takeuchi K: Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging. Role of capsaicin-sensitive sensory neurons. Dig Dis Sci 41:339–345, 1996
Uchida M, Kawano O, Misaki N, Saitoh K, Irino O: Healing of acetic acid-induced gastric ulcer and gastric mucosal PGI2 level in rats. Dig Dis Sci 35:80–85, 1990.
Smith GJM, Lefebvre RA: Influence of age on responsiveness of gastric fundus to agonists and to stimulation of intrinsic nerves. Eur J Pharmacol 223:97–102, 1992
Li DS, Rayboul, HE, Quintero E, Gout, P: Calcitonin-gene related peptide mediates the gastric hyperemic response to acid back diffusion. Gastroenterology 102:1124–1128, 1992
Whittle BJR, Lopes-Bermonte J, Moncada S: Regulation of gastric mucosal integrity by endogenous nitric oxide: interaction with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 99:607–611, 1990
Gyires K, Müllner K, Rónai AZ: Functional evidence that gastroprotection can be induced by activation of central alpha 2B-adrenoceptor subtypes in the rat. Eur J Pharmacol 396:131–135, 2000
Gyires K, Rónai AZ, Müllner K, Fürst S: Intracerebroventricular injection of clonidine releases β-endorphin to induce mucosal protection in the rat. Neuropharmacology 39:961–968, 2000
Gyires K: Morphine inhibits the ethanol-induced gastric damage in rats. Arch Int Pharmacodyn 306:170–181, 1990
Gyires K: The role of endogenous nitric oxide in the gastroprotective action of morphine. Eur J Pharmacol 255:33–37, 1994
Gyires K, Rónai AZ, Tóth G, Darula Zs, Fürst S: Analysis of the role of δ opioid receptors in gastroprotection in the rat. Life Sci 60:1337–1347, 1997
Gyires K, Rónai AZ: Supraspinal δ-and μ-opioid receptors mediate gastric mucosal protection in the rat. J Pharmacol Exp Ther 297:1010–1015, 2001
Zsilla G, Zelles T, Mike A, Kékes-Szabó A, Milusheva E, Vizi ES: Differential changes in presynaptic modulation of transmitter release during aging. Int J Dev Neurosci 12:107–115, 1994.
Crisp T, Stafinsky DL, Hoskins DL, Perni VC, Uram M, Gordon TL: Age-related changes in the spinal antinociceptive effects of DAGO, DPDPE and β-endorphin in the rat. Brain Res 643:282–286, 1994
Noble EP, Wurtman RJ, Axelrod J: A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain. Life Sci 6(3):281–291, 1967
Ueda H, Amano H, Shiomi H, Takagi H: Comparison of the analgesic effects of various opioid peptides by a newly devised intracisternal injection technique in conscious mice. Eur J Pharmacol 56:265–268, 1979
D'Amour FE, Smith DL: A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–78, 1941
Rónai AZ, Gyires K, Barna I, Müllner K, Palkovics M: Neonatal monosodium glutamate treatment abolishes both delta opioid receptor-induced and alpha-2 adrenoceptor-mediated gastroprotection in the rat lower brainstem in rats. J Physiol (Paris) 95:215–220, 2001
Masuda Y, Ohno T, Uramoto H, Ishihara T: Effects of aging on gastric secretion and blood flow in rats. In Mechanism of Injury, Protection and Repair of the Upper Gastrointestinal Tract. A Garner, PR O'Brien (eds). Chichester, John Wiley & Sons, 1990, pp 309–317
Mejmudar APN, Moshier JA, Arlow FL, Luk GD: Biochemical changes in the rat gastric mucosa after injury in young and aged rats. Biochim Biophys Acta 992:35–40, 1989
Santer RM, Baker DM: Enteric neuron numbers and sizes in Auerbach's plexus in small and large intestines of adult and aged rats. J Auton Nerv Syst 25:59–67, 1988
Guidobono F, Pagani F, Ticozzi C, Netti C: Investigation on the mechanisms involved in central protective effect of amylin on gastric ulcers in rats. Br J Pharmacol 125:23–28, 1998
Kato K, Yang H, Tache Y: Low dose of TRH act in the dorsal motor nucleus to induce gastric protection in rats. Am J Physiol 269:R1301–R1307, 1995
Király Á, Süto G, Tache Y: Role of nitric oxide in the gastric protection induced by central vagal stimulation. Eur J Pharmacol 240:299–300, 1993
Tache Y, Yoneda M, Kato K, Király Á, Süto G, Kaneko H: Intracisternal thyreotropin-releasing hormon-induced vagally mediated gastric protection against ethanol lesions: central and peripheral mechanism. J Gastroentrol Hepatol 9(suppl. 1):S29–S35, 1994
Yang H, Kawakubo K, Tache Y: Intracisternal PYY increases gastric mucosal resistance: role of cholinergic, CGRP and NO pathways. Am J Physiol 277:G555–G562, 1999
Nishimura E, Buchan AMJ, McIntosh CHS: Autoradiographic localization of opioid receptors in the rat stomach. Neurosci Lett 50:73–78, 1984
Nishimura E, Buchan AMJ, McIntosh CH: Autoradiographic localization of μ-and δ-type opioid receptors in the gastrointestinal tract of the rat and guinea pig. Gastroenterology 91:1084–1094, 1986
Hoskins DL, Gordon TL, Crisp T: The effects of aging on mu and delta opioid receptors in the spinal cord of Fischer-344 rats. Brain Res 791:299–302, 1998
Messing RB, Vasquez BJ, Samaniego B, Jensen RA, Martinez JL, McGaugh JL: Alteration in dihydromorphine binding in cerebral hemispheres of aged male rats. Neurochemistry 36:784–787, 1981
Piva F, Celotti F, Dondi D, Limonta P, Maggi R, Messi E, Negri-Cesi P, Zanisi M, Motta M, Martini L: Aging of the neuroendocrine system in the brain of male rats: receptor mechanisms and steroid metabolism. J Reprod Fertil Suppl 46:47–59, 1993
Robert A, Nezamis JE, Lancaster C, Hanchar AJ: Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, thermal injury. Gastroenterology 77:433–443, 1979
Holzer P, Lippe IT: Stimulation of afferent endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa. Neuroscience 27:981–987, 1988
Szolcsányi J, Bartho L: Impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat. In Gastrointestinal defense mechanisms. G Mózsik, O Hanninen, O Javor (eds). Oxford and Budapest, Pergamon Press and Akadémiai Kiadó, 1981, pp 39–51
Holzer P, Sametz W: Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 91:975–981, 1986
Tache Y, Yoneda M: Central action of TRH to induce vagally mediated gastric cytoprotection and ulcer formation in rats. J. Clin. Gatsroenetrol. 17(suppl 1):S58–S63, 1993
Green T, Dockray GJ: Calcitonin gene-related peptide and substance P in afferents to the upper gastrointestinal tract in the rat. Neurosci Lett 76:151–156, 1987
Bielefeldt K, Ozaki N, Gebhart GF: Mild gastritis alters voltage-sensitive sodium currents in gastric sensory neurons in rats. Gastroenterology 122:752–761, 2002
Bielefeldt K, Ozaki N, Gebhart GF: Experimental ulcers alter voltage-dependent sodium currents in rat gastric sensory neurons. Gastroenterology 122:394–405, 2002
Szabo S, Gallagher CT, Horner HC, Frankel PW, Underwood RH, Konturek SJ, Brozowski T, Trier JS: Role of adrenal cortex in gastric mucosal protection by prostaglandins, sulfhydryls, and cimetidine in the rat. Gastroenterology 85:1384–1390, 1983
Gidner S, Koyoncuoglu M, Gelai A, Gumustekin M, Guven H, Bokesoy A, Gure A: Circadian rytmicity in serotonine-induced acute gastric mucosal injury in rats. Int J Exp Pathol 79(2):105–108, 1998
Filaretova LP, Filaretov AA, Makara GB: Corticosterone increase inhibits stress-induced gastric erosions in rats. Am J Physiol 274(6Pt 1):G1024–G1030, 1998
Snyder SH: A multiplicity of opiate receptors and enkephalin neuronal systems. J Clin Psychiatry 43:9–16, 1982
Sulaiman MR, Dutia MB: Opioid inhibition of rat medial vestibular neurons in vitro and its dependence on age. Exp Brain Res 122(2):196–202, 1998
Hoskins B, Burton CK, Ho IJK.: Differences in morphineinduced antinociception and locomotor activity in mature adult and aged mice. Pharmacol Biochem Behav 25:599–605, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gyires, K., Barna, I. Differences in Gastroprotective Processes in 6- to 8- and 14- to 16-Week-Old Rats. Dig Dis Sci 47, 2775–2782 (2002). https://doi.org/10.1023/A:1021073609639
Issue Date:
DOI: https://doi.org/10.1023/A:1021073609639