Dual modulation of the L-type calcium current of rat osteoblastic cells by parathyroid hormone: opposite effects of protein kinase C and cyclic nucleotides.
Using whole-cell voltage-clamp recording of rat osteoblastic cells, we show that PTH-(1-34), known to stimulate protein kinase C (PKC) and adenylate cyclase, has a dual effect on the L-type calcium current. It induces a long-lasting increase and a superimposed reversible decrease, which can be separated by repeating hormone applications. The stimulatory effect is the only effect induced by the (3-34) fragment, able to stimulate PKC but unable to stimulate adenylate cyclase. The L current is stimulated by an active phorbol ester and is reduced by permeable analogues of cyclic AMP. Thus, the effect of PTH-(1-34) can be explained by the opposite effects of PKC and cyclic AMP. Dibutyryl cyclic GMP reduces the L current even more potently than dibutyryl cyclic AMP. The above modulations are all voltage-insensitive. These results led us to reinvestigate the effects of some vitamin D3 metabolites known to stimulate PKC and/or guanylate cyclase, and previously reported to affect the voltage-sensitivity of the L current. We only detected voltage-insensitive effects.
Laboratoire des Tissus Calcifiés, Hôpital des Enfants-Malades, Paris, France.
J
J
Fritsch
D
D
Chesnoy-Marchais
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology*; D051381:Rats
D015220:Calcium Channels; D009712:Nucleotides, Cyclic; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D002762:Cholecalciferol; D011493:Protein Kinase C; D002118:Calcium