Possible involvement of ryanodine receptor-mediated intracellular calcium release in the effect of corticotropin-releasing factor on adrenocorticotropin secretion.

We examined the role of intracellular calcium release in the regulation of CRH-induced ACTH secretion using the AtT20 corticotroph cell line. We found that ruthenium red, an inhibitor of ryanodine receptor, substantially diminished the secretory response, whereas Xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, had no effect. Expression of two ryanodine receptor subtypes (RyR1 and RyR3) was confirmed by RT-PCR. We also found that caffeine, a ryanodine receptor agonist, significantly stimulated, whereas thapsigargin, which causes depletion of intracellular calcium store, markedly diminished, the ACTH release. These results suggest that ryanodine receptor-mediated calcium-induced calcium release is involved in the regulation of CRH-induced ACTH release.