Effect of cholinergic agonists on gastrin release from primary cultures of human antral G cells.

Abstract

There is conflicting evidence concerning whether muscarinic regulation of gastrin release in humans is a direct or indirect effect on antral G cells. The present experiments were designed to resolve this question using an isolated human G-cell preparation. The ability of muscarinic agonists to stimulate or inhibit gastrin release was assessed with or without an immunoneutralizing somatostatin antibody or an m3 receptor antagonist. The effect of secretogogues on G and D cells was monitored by intracellular calcium imaging. Muscarinic agonists failed to stimulate gastrin release, even after the removal of somatostatin-induced inhibition. Our group has previously shown that muscarinic agonists stimulated somatostatin release from antral D cells. Methacholine (100 mumol/L) increased intracellular calcium levels in cocultured D cells; this increase was inhibited by the m3 receptor antagonist 4-diphenylacetoxy-n-methylpiperidine methiodide. Gastrin cells in the same field of view lacked a response to methacholine but showed a clear response to 10 nmol/L bombesin. The experiments indicate that vagal control of gastrin release in humans is indirect; stimulation would be achieved by the activation of intrinsic gastrin-releasing peptide neurons, and inhibition would be via the paracrine action of somatostatin released from adjacent D cells.