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

Abstract

SUMMARY1. Sialoadenectomized and sham-operated rats were given salivary secretary stimulants 30 min prior to intragastric instillation of a bile salt solution (5 mM-sodium taurocholate in 100 mM-HCl).2. Administration of the ac-agonist phenylephrine (015-15 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 shamsialoadenectomized rat. The effect was not apparent if the salivary glands had been previously excised.3. 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.4. Administration of secretary 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.5. The protective action of phenylephrine in sham-sialoadenectomized rats was reversed by prior treatment with the a-antagonist, phentolamine (2 mg/kg). The effect of phentolamine was dose dependent.6. Vagotomy abolished the protective influence of phenylephrine in shamsialoadenectomized rats but did not influence the response to other salivary secretary stimulants consistently.7. These data suggest that stimulation of ox-adrenergic receptors in rat salivary tissue is associated with an amelioration ofthe increase in gastric mucosal permeability to H+, Na+ and K+ in response to an intraluminal bile salt solution. The apparent protective influence of a-adrenergic receptor activation in sham-sialoadenectomized rats is mediated in part by the vagus nerve.