Muscarinic receptor stimulation induced oscillatory and monophasic Ca2+ transients in rat adrenal chromaffin cells in the absence of external Ca2+. As this Ca2+ mobilization may be mediated by InsP(3), we first explored types of InsP(3) receptors and their intracellular distribution in chromaffin cells. The InsP(3) receptor type 1 was not immunodetected in precipitates of adrenal medulla homogenates and in dissociated adrenal chromaffin cells, whereas an anti-type 3 mAb recognized a faint band with about 250 kDa, but no significant immumoreaction was visible in chromaffin cells. The anti-type 2 mAb strongly detected a band with about 220 kDa and the immunoreaction was observed perinuclearly and at the cell periphery. These results indicate that InsP(3) receptor type 2 is predominant in chromaffin cells. The oscillatory and monophasic Ca2+ transients were reproduced in simulation based on a three-state kinetic model (shut, open, and inactivated states). Ca2+ ions were found experimentally and theoretically to turn over rapidly between stores and the cytosol during stimulation. The results suggest that InsP(3) receptor type 2 is responsible for both oscillatory and monophasic Ca2+ transients and that change in mode of Ca2+ responses may be accounted for by the kinetic property of the type 2 receptor. (C) 2003 Elsevier Ltd. All rights reserved.