Details

Autor(en) / Beteiligte

• Hirasawa, Takae
• Nakamura, Takeshi
• Mizushima, Akiko
• Morita, Mitsuhiro
• Ezawa, Ikuko
• Miyakawa, Hiroyoshi
• Kudo, Yoshihisa

Titel

Adverse effects of an active fragment of parathyroid hormone on rat hippocampal organotypic cultures

Ist Teil von

• British journal of pharmacology, 2000-01, Vol.129 (1), p.21-28

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• Adverse effects of an active fragment of parathyroid hormone (PTH1–34), a blood Ca2+ level‐regulating hormone, were examined using rat hippocampal slices in organotypic culture. Exposure of cultured slice preparations to 0.1 μM PTH1–34 for 60 min resulted in a gradual increase in the intracellular Ca2+ concentration ([Ca2+]i); this effect was most obvious in the apical dendritic region of CA1 subfield. When PTH1–34 at a lower concentration (1 nM) was added to the culture medium and its toxic effects examined using a propidium iodide intercalation method, significant toxicity was seen 3 days after exposure and increased with time. Cells in the CA1 region seemed more vulnerable to the hormone than cells in other regions. At 1 week of exposure, the toxic effects were dose‐dependent over the range of 0.1 pM to 0.1 μM, the minimum effective dose being 10 pM. The adverse effects were not induced either by the inactive fragment, PTH39–84, or by an active fragment of PTH‐related peptide (PTHrP1–34), an intrinsic ligand of the brain PTH receptor. The PTH1–34‐induced adverse effects were significantly inhibited by co‐administration of 10 μM nifedipine, an L‐type Ca2+ channel blocker, but not by co‐administration of blockers of the other types of Ca2+ channel. The present study demonstrates that sustained high levels of PTH in the brain might cause degeneration of specific brain regions due to Ca2+ overloading via activation of dihydropyridine‐sensitive Ca2+ channels, and suggests that PTH may be a risk factor for senile dementia. British Journal of Pharmacology (2000) 129, 21–28; doi:10.1038/sj.bjp.0702949