Dissociation of phosphaturia and 25(OH)D-1 alpha-hydroxylase trophism using a novel analogue of parathyroid hormone
| Autor: | Thomas O. Carpenter, M. D. McPhee, D. L. Carnes, R. Bort, Mary Ann Mitnick |
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| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
Physiology Ratón Endocrinology Diabetes and Metabolism Parathyroid hormone Phosphates D-1 Mice Physiology (medical) Internal medicine Cyclic AMP Vitamin D and neurology medicine Animals chemistry.chemical_classification Kidney Phosphorus Metabolism Mice Inbred C57BL Enzyme medicine.anatomical_structure Endocrinology chemistry Parathyroid Hormone Steroid Hydroxylases Cholestanetriol 26-Monooxygenase Calcium Physiological actions |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 262:E483-E487 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.1992.262.4.e483 |
| Popis: | Certain parathyroid hormone (PTH) analogues have been shown to selectively impair some but not all physiological actions of PTH. In this study, transaminated rat (r) PTH [TA-rPTH-(1-34)], a PTH analogue that differs from the rPTH-(1-34) fragment in that the NH2-terminal alanine is converted to pyruvate, was infused into mice to determine its properties in vivo and specifically to determine whether stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity was more dependent on concomitant renal handling of phosphate or on generation of adenosine 3',5'-cyclic monophosphate (cAMP). High-performance liquid chromatography-purified TA-rPTH-(1-34) was infused into C57BL mice at 10 or 30 pmol/h for 24 h. At 30 pmol/h, TA-rPTH-(1-34) was comparable with rPTH-(1-34) in its hypophosphatemic and phosphaturic effects but was less potent than rPTH-(1-34) in raising serum calcium. TA-rPTH-(1-34) was markedly less effective in stimulating renal 1 alpha-hydroxylase than rPTH-(1-34). Stimulation of urinary cAMP excretion occurred after infusion with TA-rPTH-(1-34), but this effect was significantly less than that seen with rPTH-(1-34). These findings indicate that PTH-induced hypophosphatemia and phosphaturia can be uncoupled from PTH stimulation of 1 alpha-hydroxylase. Furthermore, cAMP-related signal transduction appears to be more significant in regulation of 1 alpha-hydroxylase than mechanisms that mediate PTH-sensitive phosphate transport, independent of cAMP. |
| Databáze: | OpenAIRE |
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