The effect of adrenergic, cholinergic and peptidergic salivary stimulants on gastric mucosal integrity in the rat.

Sialoadenectomized and sham-operated rats were given salivary secretory stimulants 30 min prior to intragastric instillation of a bile salt solution (5 mM-sodium taurocholate in 100 mM-HCl). Administration of the alpha-agonist phenylephrine (0.15-15 mg/kg) resulted in a dose-dependent reduction in the loss of H+ and the intraluminal appearance of Na+ and K+ associated with bile-salt-induced damage to the stomach in the sham-sialoadenectomized rat. The effect was not apparent if the salivary glands had been previously excised. Adrenaline (0.8-4.0 mg/kg) and noradrenaline (0.8-4.0 mg/kg) were less effective in reducing the degree of mucosal damage in sham-sialoadenectomized rats and were not effective in sialoadenectomized rats. Administration of secretory stimulant doses of isoprenaline (5 mg/kg), pilocarpine (2 mg/kg) and substance P (25 mg/kg) either had no significant effect or exacerbated the net transmucosal fluxes of H+, Na+ and K+ associated with bile salt damage to the gastric mucosa. The protective action of phenylephrine in sham-sialoadenectomized rats was reversed by prior treatment with the alpha-antagonist, phentolamine (2 mg/kg). The effect of phentolamine was dose dependent. Vagotomy abolished the protective influence of phenylephrine in sham-sialoadenectomized rats but did not influence the response to other salivary secretory stimulants consistently. These data suggest that stimulation of alpha-adrenergic receptors in rat salivary tissue is associated with an amelioration of the increase in gastric mucosal permeability to H+, Na+ and K+ in response to an intraluminal bile salt solution. The apparent protective influence of alpha-adrenergic receptor activation in sham-sialoadenectomized rats is mediated in part by the vagus nerve.