Role of β-Adrenoceptors in Gastric Mucosal Integrity and Gastroprotection Induced by Epidermal Growth Factor

Abstract

The central and peripheral adrenergic systems are involved in the regulation of gastric secretion but little is known about the role of α- and β-adrenoceptors in gastroprotection. In this study, acute gastric lesions were produced by an intragastric (i.g.) application of 100% ethanol and gastric blood flow (GBF) was determined by H₂-gas clearance technique in rats with or without i.g. or intraperitoneal (i.p.) administration of α- or β-adrenoceptor agonists or antagonists. Phenylephrine, α₁-adrenergic agonist, and clonidine, α₂-agonist, significantly augmented the ethanol-induced lesions while decreasing the GBF and these effects were reversed by the blockade of α₁-adrenoceptors with prazosin and α₂-adrenoceptors with yohimbine. In contrast, isoproterenol (ISO) (0.01-10 mg/kg i.g.), β-adrenoceptor agonist, reduced dose-dependently ethanol-induced mucosal injury and this effect was accompanied by an elevation of the GBF similarly as after epidermal growth factor (EGF) (100 μg/kg·h s.c.) or after classic protective agent, 16,16-dimethyl-PGE₂ (PGE₂) (10 μg/kg i.g.). The pretreatment with β-antagonist, propranolol, diminished the protective and hyperemic effects of ISO and EGF but failed to affect those induced by PGE₂. Suppression of nitric oxide (NO) synthase activity by L-NAME or sensory denervation with capsaicin attenuated significantly the ISO- and EGF-induced gastroprotection and elevation of GBF, whereas the inhibition of PG biosynthesis by indomethacin remained without any significant effect. Adrenal medullectomy or chemical sympathectomy by 6-hydroxydopamine by itself failed to influence significantly the ethanol-induced damage but completely abolished the protective and hyperemic effects of EGF being without any influence on those induced by PGE₂. ISO combined with EGF, restored the protective and hyperemic effects of this peptide in medullectomized rats. We conclude that (1) local activation of β-adrenoceptors by ISO affords protection and elevation of GBF, both these effects being mediated by arginine-NO pathway and sensory nerves and (2) sympathetic system and adrenal medulla contribute to the protective and hyperemic activity of EGF.

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

“…Similarly, taurine had no significant effect on the increased gastric acidity reported in alendronate-induced gastric damage in rats [36]. The gastroprotective effects of spermine [37] and taurine [36] as represented by reduction in GUI were previously demonstrated. The suppression of acid secretion by spermine might be attributed to uncoupling of the gastric K + /H + exchange pump in the secretory membrane, thus decreasing the ATPase-mediated uptake of H + .…”

Central Leptin and Cholecystokinin in Gastroprotection against Ethanol-Induced Damage

“…prior to leptin or CCK markedly attenuated the gastroprotection afforded by these peptides and that the addition of L -arginine, the substrate for NOS [28, 29], restored the protective activity of leptin or CCK-8. The notion that NO contributes to the protective activity of leptin and CCK was supported by our finding that the common feature of both leptin and CCK was a significant rise in gastric luminal production of NO that might contribute to the protective and hyperemic effects of both these hormonal peptides.…”

“…application of 75% ethanol similar to the method described previously by our group using ethanol as a damaging agent [17, 28, 29]. Briefly, 75% ethanol in a volume of 1.5 ml was administered i.g.…”

“…The luminal concentration of NO was quantified indirectly as nitrate (NO – 3 ) and nitrite (NO – 2 ) levels in the gastric contents using the nitrate/nitrite kit purchased from Cayman Lab (Ann Arbor, Mich., USA) as recently described in detail [29]. This method is based on the Griess reaction and generation of chromophore absorbing at 595 nm, according to the original procedure described previously [36].…”

Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa

“…Agonists of ␤-adrenoceptors (Brzozowski et al, 1997c) Capsaicin Central vagal stimulation (Tache et al, 1994) Papaverin ) Pathological circumstances Anaemia (Casadevall et al, 1994) Endotoxemia (Brzozowski et al, 1997b) Mild irritants Portal hypertension (Calatayud et al, 2001) Uremia (Quintero and Guth, 1992) with the nature of injury, a reduced accumulation of inflammatory cells in the mucosa seems likely to be implicated (see Immune System). Other possible mechanisms involved specifically in NSAID's action include modulation of the effects of vasoconstrictor substances, i.e., endothelin (López-Belmonte et al, 1993) or prevention of the focal ischaemias induced by the increase in contractility that accompanies lesion development (Martínez-Cuesta et al, 1996a).…”