An Excessive Accumulation of Olfactory Calcium and Inhibition of Olfactory Signal Transduction by Organotin Compounds

Abstract

Deficiencies and excesses of trace elements induce various kinds of brain lesion. In this study, a tributyltin-induced olfactory lesion (anosmia) was examined by the kinetic analysis of the mechanisms in an excessive accumulation of calcium into the olfactory bulb, an inhibition of olfactory signal transduction and toxic cell death (necrosis or apoptosis).

The trialkyltin-induced excessive increase of calcium in the olfactory bulb was associated with an increase of olfactory PTH. Since the IP₃ level in the olfactory significantly decreased under the tributyltin exposure, which seems to be a consequence of tributyltin-induced inhibition of PI turnover, the excessive increase of olfactory calcium was not due to an influx of Ca²⁺ mediated by a plasma membrane IP₃-gated Ca²⁺ channel and a release of intracellular Ca²⁺ mediated by IP₃ receptor-channel complex from endoplasmic reticulum. The tributyltin-induced excessive increase of olfactory calcium is perhaps caused by an excessive increase in the formation of cAMP mediated by activation of adenyl cyclase and an excessive influx of extracellular Ca²⁺ mediated by cAMP-activated channels. Moreover, this rapid and excessive increase in the concentration of intracellular Ca²⁺ seems to inhibit CaM kinase II functions leading to necrosis in vivo or toxic cell death in vitro.