Interaction between endogenous opioids, cholinergic and adrenergic mechanisms during vagally-induced gastrin release in rats

Endogenous opioids are present in neurons of the vagus and the intrinsic nervous system and they are colocalized with gastrin in antral G-cells. This raises the possibility that endogenous opioids modulate gastrin release. Stimulation of both cervical vagi (10V, 5Hz, 5ms) elicited an increase of arterial plasma gastrin levels at intragastric pH7 or pH2. The response at pH2 was 30% of that at luminal pH7. Atropine reduced vagally stimulated gastrin levels substantially. At luminal pH2 the small residual noncholinergic response was mediated neither by adrenergic mechanisms nor by endogenous opioids. At luminal pH 7 adrenergic blockade with phentolamine and propranolol reduced vagally stimulated gastrin by 60%. In the presence of atropine adrenergic blockade elicited only a small inhibitory effect suggesting that vagal activation of adrenergic mechanisms depends on atropine-sensitive cholinergic pathways. Blockade of opiate receptors by naloxone had no effect on vagal gastrin release, however, the noncholinergic gastrin response was reduced significantly by naloxone, suggesting that cholinergic mechanisms normally restrain activation of endogenous opioids during vagal stimulation. Naloxone had no effect on the noncholinergic, nonadrenergic stimulation of gastrin levels. These data suggest that endogenous opioids can contribute to vagal gastrin release provided the cholinergic restraint is blocked and adrenergic mechanisms stimulate endogenous opioids. In conclusion a major role of endogenous opioids in the regulation of vagal gastrin release can not be detected.