The effect of retinoic acid on parathyroid hormone- and parathyroid hormone-related peptide-induced intracellular calcium in a rat osteosarcoma cell line, UMR106.
We have examined the effects of parathyroid hormone (PTH) and PTH-related peptide (PTH-rP) on intracellular calcium (Ca2+i) in a rat osteogenic sarcoma cell line, UMR106. Synthetic bovine (b)PTH(1-34) caused a small inconsistent rise in Ca2+i in UMR106 cells, whilst cells pretreated with retinoic acid (RA, 1 mumol/l) for 18 h exhibited reproducible, significant and dose-dependent increases in Ca2+i levels in response to bPTH. The effect of RA on PTH-induced changes in Ca2+i were dependent upon both dose and time. Purified human (h)PTH-rP(1-34) increased Ca2+i in the absence of RA in the same cells. However, RA increased the magnitude of PTH-rP-stimulated changes in Ca2+i without affecting the concentration required for a maximal response. RA also prolonged the delay before the Ca2+i response was observed. Maximal responses to PTH-rP were greater in magnitude than those to PTH. These changes appeared not to be due to cyclic AMP (cAMP), since neither dibutyryl cAMP (1 mmol/l) nor forskolin (15 mumol/l) affected Ca2+i. PTH- and PTH-rP-mediated Ca2+i transients were not completely abolished by the absence of extracellular calcium, and both peptides increased basal levels of inositol trisphosphate. PTH and PTH-rP were subject to mutual desensitization, but were not desensitized by prostaglandin E2. PTH(7-34) antagonized PTH- but not PTH-rP-mediated Ca2+i transients. We conclude that there may be some important differences in the mechanism of action of PTH and PTH-rP.
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A D
AD
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School.
Brown
B L
BL
Dobson
P R
PR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); C064776:parathyroid hormone-related protein (7-34)amide; C025076:parathyroid hormone (1-34), bovine; D014212:Tretinoin; D002118:Calcium