Adaptive cytoprotection is a concept to counteract against the gastric mucosal injury caused by stress, strong irritants and drugs such as non-steroidal anti-inflammatory drugs. The process is mediated through diverse mediators and mechanisms. Studies on adaptive cytoprotection began from the discovery of prostaglandin (PG)-dependent and PG-independent pathways, followed by the investigation on the types and concentrations of mild irritants to be used. Upon the confirmation on the importance of the vagus nerve and the vago-vagal pathway in regulating the mucosal protective actions of the mild irritants, individual participating mediators for the neuronal modulatory processes were explored, including peptide neurotransmitters such as calcitonin gene-related peptide and substance P. Further correlation with the sympathetic nervous system, the sensory afferent neurons and the enteric nervous system of the gastric mucosa had been made. A close working relationship between the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the enteric nervous system was then proposed, with concurrent regulation of PG, nitric oxide and sensory neuropeptides by different mild irritants. Apart from these conventional concepts, there are now contemporary ideas on newer forms of adaptive cytoprotection such as ischemic preconditioning and heat-shock proteins, which will cast new light to novel approaches in facilitating gastric mucosal protection.

1.
Robert A, Nezamis JE, Lancaster C, Hanchar AJ: Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 1979;77:433–443.
[PubMed]
2.
Szabo S: Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis: a primer for cytoprotection-organoprotection. Klin Wochenschr 1986;64(suppl 7):116–122.
[PubMed]
3.
Chaudhury TK, Robert A: Prevention by mild irritants of gastric necrosis produced in rats by sodium taurocholate. Dig Dis Sci 1980;25:830–836.
[PubMed]
4.
Konturek SJ, Brzozowski T, Piastucki I, Radecki T, Dembinski A, Dembinska-Kiec A: Role of locally generated prostaglandins in adaptive gastric cytoprotection. Dig Dis Sci 1982;27:967–971.
[PubMed]
5.
Foschi D, Castoldi L, del Soldato P, Musazzi M, Callioni F, Rovati V, Trabucchi E, Montorsi W: Effects of autonomic nervous system on gastric damage by ethanol in the rat. Dig Dis Sci 1989;34:688–693.
[PubMed]
6.
Holzer P, Sametz W: Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 1986;91:975–981.
[PubMed]
7.
Holzer P, Guth PH: Neuropeptide control of rat gastric mucosal blood flow: increase by calcitonin gene-related peptide and vasoactive intestinal polypeptide, but not substance P and neurokinin A. Circ Res 1991;68:100–105.
[PubMed]
8.
Stead RH, Dixon RF, Bramwell NH: Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology 1989;97:575–585.
[PubMed]
9.
Whittle BJR, Lopez-Belmonte J, Moncada S: Regulation of gastric mucosal integrity by endogenous nitric oxide: interaction with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 1990;99:607–611.
[PubMed]
10.
Esplugues JV, Whittle BJR, Moncada S: Modulation by opioids and by afferent sensory neurons of prostanoid protection of the rat gastric mucosa. Br J Pharmacol 1992;106:846–852.
[PubMed]
11.
Cho CH, Ogle CW: The effect of zinc sulphate on vagally-induced mast cell changes and ulcers in the rat stomach. Eur J Pharmacol 1976;43:315–322.
12.
Henagan JM, Smith GS, Seidel ER, Miller TA: Influence of vagotomy on mucosal protection against alcohol-induced gastric damage in the rat. Gastroenterology 1984;87:903–908.
[PubMed]
13.
Cho CH, Chen BW, Hui WM, Lam SK, Ogle CW: The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats. J Gastroenterol Hepatol 1992;7:178–183.
[PubMed]
14.
Okumura T, Uehara A, Okumura K, Namiki M: Site-specific formation of gastric ulcers by the electric stimulation of the left or right gastric branch of the vagus nerve in the rat. Scand J Gastroenterol 1990;25:834–840.
[PubMed]
15.
Ko JKS, Cho CH, Ogle CW: The vagus nerve and its non-cholinergic mechanism in the modulation of ethanol-induced gastric mucosal damage in rats. J Pharm Pharmacol 1994;46:29–32.
[PubMed]
16.
Sikiric P, Rotkvic I, Mise S, Krizanac S, Suchanek E, Petek M, Gjuris V, Geber J, Tucan-Foretic M, Udovicic I, Anic T, Balen I: The influence of dopamine agonists and antagonists on gastric lesions in mice. Eur J Pharmacol 1987;144:237–239.
[PubMed]
17.
Ko JKS, Cho CH: The mechanistic pathway of gastric adaptive cytoprotection: a study on different components of the autonomic nervous system. J Auton Pharmacol 1995;15:205–214.
[PubMed]
18.
Bhandare PN, Rataboli V, d’Souza RSD: Dual action of clonidine on ethanol-induced gastric lesions: is the imidazoline-preferring receptor involved? Eur J Pharmacol 1991;199:243–245.
[PubMed]
19.
Yonei Y, Holzer P, Guth PH: Laparotomy-induced gastric protection against ethanol injury is mediated by capsaicin-sensitive sensory neurons. Gastroenterology 1990;99: 3–9.
[PubMed]
20.
Ottaway CA: Role of the neuroendocrine system in cytokine pathways in inflammatory bowel disease. Aliment Pharmacol Ther 1996;10(suppl 2):10–15.
[PubMed]
21.
Filaretova LP, Podvigina TT, Bobryshev PY, Bagaeva TR, Tanaka A, Takeuchi K: Hypothalamic-pituitary-adrenocortical axis: the hidden gold in gastric mucosal homeostasis. Inflammopharmacology 2006;14:207–213.
[PubMed]
22.
Evagelista S, Maggi CA, Meli A: Lack of influence of capsaicin-sensitive sensory fibers on adaptive cytoprotection in rat stomach. Dig Dis Sci 1988;33:1050–1051.
23.
Hatakeyama Y, Tomoi M, Ohtsuka M, Shimomura K: Implication of sensory neurons in the diverse mechanisms of adaptive cytoprotection in the rat stomach. Jpn J Pharmacol 1996;70:347–350.
[PubMed]
24.
Uchida M, Yano S, Watanabe K: The role of capsaicin-sensitive afferent nerves in protective effect of capsaicin against absolute ethanol-induced gastric lesions in rats. Jpn J Pharmacol 1991;55:279–282.
[PubMed]
25.
Holzer P, Pabst MA, Lippe ITH, Peskar BM, Peskar BA, Livingston EH, Guth PH: Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology 1990;98:838–848.
[PubMed]
26.
Taché Y, Yoneda M, Kato K, Király A, Sütö G, Kaneko H: Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: central and peripheral mechanisms. J Gastroenterol Hepatol 1994;9(suppl 1):S29–S35.
[PubMed]
27.
Ohno BK, Saeki T, Hayashi H, Hayashi I, Katori M, Murata T, Narumiya S, Saigenji K, Majima M: Adaptive cytoprotection mediated by prostaglandin I2 is attributable to sensitization of CRGP-containing sensory nerves. Gastroenterology 2001;120:134–143.
[PubMed]
28.
Pajdo R, Brzozowski T, Konturek PC, Kwiecien S, Konturek SJ, Sliwowski Z, Pawlik M, Ptak A, Drozdowicz D, Hahn EG: Ischemic preconditioning, the most effective gastroprotective intervention: involvement of prostaglandins, nitric oxide, adenosine and sensory nerves. Eur J Pharmacol 2001;427:263–276.
[PubMed]
29.
Horowitz M, Assadi H: Heat acclimation-mediated cross-tolerance in cardioprotection: do HSP70 and HIF-1α play a role? Ann NY Acad Sci 2010;1188:199–206.
[PubMed]
30.
Rokutan K, Hirakawa T, Teshima S, Nakano Y, Miyoshi M, Kawai T, Konda E, Morinaga H, Nikawa T, Kishi K: Implications of heat shock/stress proteins for medicine and disease. J Med Invest 1998;44:137–147.
[PubMed]
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