{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:39:45Z","timestamp":1789389585359,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3317,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Adverse effects of an active fragment of parathyroid hormone (PTH<jats:sub>1\u201334<\/jats:sub>), a blood Ca<jats:sup>2+<\/jats:sup> level\u2010regulating hormone, were examined using rat hippocampal slices in organotypic culture.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Exposure of cultured slice preparations to 0.1\u2003\u03bc<jats:sc>M<\/jats:sc> PTH<jats:sub>1\u201334<\/jats:sub> for 60\u2003min resulted in a gradual increase in the intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>); this effect was most obvious in the apical dendritic region of CA1 subfield.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When PTH<jats:sub>1\u201334<\/jats:sub> at a lower concentration (1\u2003n<jats:sc>M<\/jats:sc>) 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\u2010dependent over the range of 0.1\u2003p<jats:sc>M<\/jats:sc> to 0.1\u2003\u03bc<jats:sc>M<\/jats:sc>, the minimum effective dose being 10\u2003p<jats:sc>M<\/jats:sc>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The adverse effects were not induced either by the inactive fragment, PTH<jats:sub>39\u201384<\/jats:sub>, or by an active fragment of PTH\u2010related peptide (PTHrP<jats:sub>1\u201334<\/jats:sub>), an intrinsic ligand of the brain PTH receptor.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The PTH<jats:sub>1\u201334<\/jats:sub>\u2010induced adverse effects were significantly inhibited by co\u2010administration of 10\u2003\u03bc<jats:sc>M<\/jats:sc> nifedipine, an L\u2010type Ca<jats:sup>2+<\/jats:sup> channel blocker, but not by co\u2010administration of blockers of the other types of Ca<jats:sup>2+<\/jats:sup> channel.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study demonstrates that sustained high levels of PTH in the brain might cause degeneration of specific brain regions due to Ca<jats:sup>2+<\/jats:sup> overloading <jats:italic>via<\/jats:italic> activation of dihydropyridine\u2010sensitive Ca<jats:sup>2+<\/jats:sup> channels, and suggests that PTH may be a risk factor for senile dementia.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 21\u201328; 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