Central neurotensin inhibits gastric acid secretion: An adrenergic mechanism in rats

Abstract

Although parenteral neurotensin (NT) inhibits stimulated gastric acid secretion, published reports on the effect of centrally administered NT on gastric acid secretion are conflicting. This study provides evidence suggesting that, in chronic gastric fistula rats, intracerebroventricularly administered NT (15–60 μg) significantly reduces both basal and pentagastrin-, 2-deoxy-d-glucose-, and carbacol- but not histamine-stimulated gastric acid secretion. Using radioimmunoassay, the concentration of plasma immunoreactive NT increased from 30 to 200 pg/ml at 30 and 60 min, respectively after a single intracerebroventricular (i.c.v.) administration of NT at a dose of 60 μg. These serum NT concentrations can be reproduced by a constant NT i.v. infusion at 2 μg/kg · h. This parenteral infusion dose does not inhibit acid secretion as does i.c.v. NT. Pretreatment with the i.c.v. dopamine-2 receptor antagonists haloperidol or domperidone totally abolishes the inhibitory effect of i.c.v. NT on pentagastrin-stimulated gastric acid secretion. In contrast, pretreatment with the specific dopamine-1 receptor antagonist SCH 23900 or the specific dopamine-2 receptor antagonist sulpiride does not affect i.c.v. NT-induced inhibition of pentagastrin-stimulated gastric acid secretion. Pretreatment (intracerebroventricularly) with the α-adrenergic antagonist phentolamine blocks the antisecretory effect of i.c.v. NT. Administration of 3.0/gmg NT per side directly into nucleus accumbens (NACB), using a stereotaxic technique, significantly reduces basal gastric acid secretion. This effect of central NT is blocked by pretreatment with intra-NACB haloperidol (0.5 μg per side). These findings suggest that NT acts centrally to inhibit gastric acid secretion, an effect that may occur within NACB and be mediated by central nervous system α-adrenergic receptor activation.