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Journal of Histochemistry and Cytochemistry, Vol. 46, 1351-1358, December 1998, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

In Vivo Dose-related Receptor Binding of the Vitamin D Analogue [3H]-1,25-dihydroxy-22-oxavitamin D3 (OCT) in Rat Parathyroid, Kidney Distal and Proximal Tubules, Duodenum, and Skin, Studied by Quantitative Receptor Autoradiography

Nobuo Koikea, Naohiko Hayakawaa, Kenji Kumakia, and Walter E. Stumpfa
a Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan

Correspondence to: Nobuo Koike, Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan..

1,25-Dihydroxy-22-oxavitamin D3 (OCT) is a new synthetic analogue of 1,25(OH)2D3 with a low calcemic effect. This study utilized quantitative receptor autoradiography to determine the dose-related receptor binding and saturation among the vitamin D target cells: parathyroid chief cells, kidney distal and proximal tubule epithelium, duodenal absorptive epithelium, and epidermal keratinocytes. Rats were injected with 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, or 16.0 µg/kg bw of [26-3H]-OCT and sacrificed 1 hr afterwards. Then autoradiographs were prepared under identical conditions. In these target cells, nuclear uptake of radioactivity increased with dose and then achieved a plateau. However, their saturation doses showed differences: parathyroid chief cells 1–2 µg; duodenal absorptive epithelium, distal tubule epithelium, and epidermal keratinocytes 4–6 µg; proximal tubule epithelium 8 µg (per kg bw). In contrast, in nontarget cells, such as liver and duodenal smooth muscle, radioactivity did not concentrate in the nuclei but increased in the cytoplasm with dose, without plateauing. These results provide the first information on the relative saturabilities of various target cell populations with a vitamin D ligand. Parathyroid chief cells required the relatively lowest receptor saturation dose. This suggests a high sensitivity and response to OCT treatment with related therapeutic potential for the regulation of parathyroid function. (J Histochem Cytochem 46:1351–1358, 1998)

Key Words: vitamin D, OCT, VDR, parathyroid, target tissue, autoradiography


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