Parathyroid hormone-related protein (PTHrP) was discovered a dozen years ago as a product of malignant tumors. It is now known that PTHrP is a paracrine factor with multiple biological functions. One such function is to relax smooth muscle by inhibiting calcium influx into the cell. In the central nervous system, PTHrP and its receptor are widely expressed in neurons in the cerebral cortex, hippocampus and cerebellum. The function of PTHrP in the CNS is not known. Previous work has shown that expression of the PTHrP gene is depolarization-dependent in cultured cerebellar granule cells and depends specifically on L-type voltage sensitive calcium channel (L-VSCC) Ca(2+) influx. PTHrP has also been found to be capable of protecting these cells against kainic acid-induced excitotoxicity. Here, we tested the idea that mice with a PTHrP-null CNS might display hypersensitivity to kainic acid excitotoxicity. We found that these mice were six-fold more sensitive than control littermate mice to kainic-acid-induced seizures as well as hippocampal c-Fos expression. PTHrP-null embryonic mixed cerebral cortical cultures were more sensitive to kainic acid than control cultures, and PTHrP addition was found to be protective against kainate toxicity in both PTHrP-null and control cultures. By whole-cell techniques, PTHrP was found to reduce L-VSCC Ca(2+) influx in cultured mouse neuroblastoma cells. We conclude that PTHrP functions as a component of a neuroprotective feedback loop that is structured around the L-type calcium channel. This loop appears to be operative in vivo as well as in vitro.
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http://dx.doi.org/10.1016/s0006-8993(01)03407-2 | DOI Listing |
Diagn Pathol
January 2025
Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
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View Article and Find Full Text PDFJ Small Anim Pract
January 2025
Department of Veterinary Medicine and Surgery, University of Missouri, College of Veterinary Medicine, Columbia, Missouri, USA.
A 9-year-old, presumed male castrated mixed breed dog was evaluated for lethargy, hyporexia, polyuria, polydipsia and diffuse gynaecomastia. Bloodwork revealed severe hypercalcaemia and hyposthenuria. CT scan showed a caudal abdominal mass consistent with a Sertoli cell tumour on cytology.
View Article and Find Full Text PDFIntroduction: Pseudohypoparathyroidism 1A (PHP1A) is the best-known representative of inactivating PTH/PTHrP signaling disorders (iPPSD). The associated phenotype develops over time and often includes hormonal resistances, short stature and osteoma cutis. More complex and very early manifestations have also been reported.
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December 2024
Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922 Alcorcón, Madrid, Spain.
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Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
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