BETHANECHOL AND A G-PROTEIN ACTIVATOR, NAF/ALCL3, INDUCE SECRETORY RESPONSE IN PANETH CELLS OF MOUSE INTESTINE

Paneth cells located at the bottom of intestinal crypts may play a role in controlling the bacterial milieu of the intestine. Using morphometry to clarify the secretory mechanism of the Paneth cells, we studied the ultrastructural changes in mouse Paneth cells produced following intra-arterial perfusion with Hanks' balanced salt solution containing a cholinergic muscarinic secretagogue (bethanechol), a neuroblocking agent (tetrodotoxin), or a G-protein activator (NAF/AlCl3). Bethanechol (2 X 10(-4) mol/l) induced Paneth-cell secretion. Many Paneth cells massively exocytosed their secretory material into the crypt lumen; the enhanced secretion caused degranulation and vacuole formation. However, tetrodotoxin (2 x 10(-6) mol/l) did not prevent the bethanechol-enhanced secretion by the Paneth cells. NaF (1 X 10(-2) mol/l) and AlCl3 (1 X 10(-5) mol/l) induced massive exocytosis of the Paneth cells; the exocytotic figures were similar to those observed in mice stimulated by bethanechol. G-protein activation was followed by a sequence of intracellular events, resulting in exocytosis.