Skip to main content
SpringerLink
Log in

Calcium regulating activity of 26,27-dialkyl analogs of 1α,25-dihydroxyvitamin D3

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

A series of analogs of 1α,25-dihydroxyvitamin D3[1,25(OH)2D3] with alkyl substitutions in 26- and 27-positions were tested for calcium (Ca) regulating activity. The potencies of dialkyl analogs in stimulating bone resorption in neonatal mouse calvaria cultures were the highest in 1α,25-dihydroxy-26,27-dimethylvitamin D3[1,25(OH)2-(Me)2D3], followed by 1,25(OH)2D3, 1α,25-dihydroxy-26,27-diethylvitamin D3[1,25(OH)2(Et)2D3], and 1α,25-dihydroxy-26,27-dipropylvitamin D3[1,25(OH)2(Pr)2D3] in that order. A similar order of potential regarding formation of osteoclast-like cells in mouse bone marrow cell cultures and on bone Ca mobilization with long-term vitamin D-deficient rats was observed in the same series. The relative potencies of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 1,25(OH)2(Et)2D3, and 1,25(OH)2(Pr)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptors were 1:1:0.16:0.036. A similar order of potential in case of intestinal Ca transport in situ was observed in the same series. The potencies of dialkyl analogs in competing with 25-hydroxy-vitamin D3 for binding to rat serum vitamin D binding protein were much lower than that of 1,25(OH)2D3. Effect of 1,25(OH)2(Me)2D3 on osteopenia in rats induced by ovariectomy and right sciatic neurotomy was higher than that of 1,25(OH)2D3. From these results, the lengthening by one carbon at 26- and 27-positions was shown to maintain the Ca regulatory activity of 1,25(OH)2D3.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Okamoto S, Tanaka Y, DeLuca HF, Kobayashi, Ikekawa N (1983) Biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3. Am J Physiol 244:E159-E163

    Google Scholar 

  2. Tanaka Y, DeLuca HF, Kobayashi Y, Ikekawa N (1984) 26,26,26, 27,27,27-Hexafluoro-1,25-dihydroxyvitamin D3: a highly potent, long-lasting analog of 1,25-dihydroxyvitamin D3. Arch Biochem Biophys 229:348–354

    Google Scholar 

  3. Eguchi T, Sai H, Takatsuto S, Hara N, Ikekawa N (1988) Synthesis of 26,27-dialkyl analogues of 1α,25-dihydroxyvitamin D3. Chem Pharm Bull 36:2303–2311

    Google Scholar 

  4. Eguchi T, Ikekawa N, Sumitani K, Kumegawa M, Higuchi S, Otomo S (1990) Effect on carbon lengthening at the side chain terminal of 1α,25-dihydroxyvitamin D3 for calcium regulating activity. Chem Pharm Bull 38:1246–1249

    Google Scholar 

  5. Shigeno C, Yamamoto I, Dokoh S, Hino M, Aoki J, Yamada K, Morita R, Kaneyama M, Torizuka K (1985) Identification of 1,24(R)-dihydroxyvitamin D3-like bone resorbing lipid in a patient with cancer-associated hypercalcemia. J Clin Endocrinol Metab 61:761–768

    Google Scholar 

  6. Takahashi N, Yamana H, Yoshiki S, Roodman GD, Munday GR, Jones ST, Boyde A, Suda T (1988) Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 122:1373–1382

    Google Scholar 

  7. Burstone MS (1958) Histochemical demonstration of acid phosphatase with naphthol AS-phosphates. J Natl Cancer Inst 21:523–539

    Google Scholar 

  8. Suda T, DeLuca HF, Tanaka Y (1970) Biological activity of 25-hydroxyergocalciferol in rats. J Nutr 100:1049–1052

    Google Scholar 

  9. Connerty HV, Briggs AR (1966) Determination of serum calcium by means of orthocresolphthalein complexone. Am J Clin Pathol 45:290–296

    Google Scholar 

  10. Omdahl J, Holick MF, Suda T, Tanaka Y, DeLuca HF (1971) Biological activity of 1,25-dihydroxycholecalciferol. Biochemistry 10:2935–2940

    Google Scholar 

  11. Okumura H, Yamamuro T, Higuchi S, Harada M, Takamura T, Otomo S, Aihara H, Ikekawa N, Kobayashi (1990) 26,27-hexafluoro-1,25-dihydroxyvitamin D3(F6-1,25(OH)2D3) prevents osteoprosis induced by immobilization combined with ovariectomy in the rat. Bone Miner 9:101–109

    Google Scholar 

  12. Seino Y, Yamaoka K, Ishida M, Yabuuchi H, Ichikawa M, Ishige H, Yoshino H, Avioli LV (1982) Biochemical characterisation of 1,25-dihydroxyvitamin D receptor in chick embryonal duodenal cytosol. Calcif Tissue Int 34:265–269

    Google Scholar 

  13. Haddad JG, Chyu KJ (1971) Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol 33:992–995

    Google Scholar 

  14. Gill HS, Londowski JM, Corrodino RA, Zmsmeister AR, Kumar R (1988) The synthesis and biological activity of 25-dihydroxy-26,27-dimethylvitamin D and 1,25-dihydroxy-26,27-dimetylvitamin D: highly potent novel analogs of vitamin D. J Steroid Biochem 31:147–160

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan

    Tatsuro Miyahara, Masaki Miyata & Hiroshi Kozuka

  2. Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, 330, Ohmiya, Saitama, Japan

    Masahiro Harada, Akemi Sugure, Yumi Ikemoto, Tadanobu Takamura, Shohei Higuchi & Susumu Otomo

  3. Department of Sciences and Technology, Iwaki Meisei University, Iwaki, Japan

    Nobuo Ikekawa

Authors
  1. Tatsuro Miyahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaki Miyata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akemi Sugure
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yumi Ikemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tadanobu Takamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shohei Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susumu Otomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Kozuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nobuo Ikekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyahara, T., Harada, M., Miyata, M. et al. Calcium regulating activity of 26,27-dialkyl analogs of 1α,25-dihydroxyvitamin D3 . Calcif Tissue Int 51, 218–222 (1992). https://doi.org/10.1007/BF00334550

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00334550

Key words

Search

Navigation