嗅覚系の異常とカルシウム局在化

抄録

Deficiency and excesses of trace elements induce various kinds of brain lesion. In this study, organotin exposure- and zinc deficiency- induced olfactory lesions were kinetically analyzed from the viewpoints of the movement of trace elements, an inhibition of signal transduction and toxic cell death (necrosis or apoptosis) in the olfactory systems.

Remarkable results were that organotin exposure and zinc deficiency induced each excessive accumulation of calcium in the olfactory system such as olfactory epithelium and olfactory bulb. This calcium localization depended upon the number and species of ligand of organotin compounds in case of organotin exposure and was parallel with the degree of manifestation of deficiency symptom in case of zinc deficiency. In case of organotin exposure, excessive increases of parathyroid hormone (PTH), cAMP and excessive decreases of inositol triphosphate (IP₃), Ca²⁺/Calmodulin-dependent protein kinase II ( CaM kinase II) were seen. In case of zinc deficiency, a remarkable decrease of PTH and a little decreases of cAMP, IP₃ were seen in the olfactory tissues, and a remarkable decrease of calcium and a remarkable increase of PTH were seen in the cerebrospinal fluid.

Putting all results together, the calcium localization in the olfactory system seems to be due to the processes such as the activation of adenylcyclase by an excessive increase of PTH in the special regions of the brain, excessive increase in the formation of cAMP by the activation of adenylcyclase, disorder of cAMP-activated channels by the excessive increasεof cAMP, and an excessive influx of extracellular Ca²⁺ by the disorder of the channels. Moreover this rapid and excessive increase in the concentration of intracellular Ca²⁺ seems to inhibit CaM kinase II functions followed by leading to necrosis or apoptosis in vivo or toxic cell death in vitro.