Parathyroid hormone stimulates electrogenic sodium transport in A6 cells.
The effects of parathyroid hormone (PTH) on sodium homeostasis in the distal tubule are not well defined. Using A6 cells as a model for distal tubular epithelium we measured equivalent short circuit current (leq), as an estimate of net sodium transport. We found that PTH increased leq in a dose-dependent manner. DDA, an agent which inhibits adenylate cyclase, decreased PTH-activated sodium transport, suggesting a role for cAMP elevation in PTH effects. Moreover, addition of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, partially blocked the PTH-stimulated leq. PTH also elicited a sustained increase in [Ca2+]i in A6 cells. This elevation in [Ca2+]i was abolished by removal of calcium from the extracellular medium, suggesting the involvement of calcium influx pathways. In fact, addition of the calcium channel blocker nitrendipine to PTH-stimulated leq partially blocked PTH-activated sodium transport. Taken together these data demonstrate that PTH stimulates electrogenic sodium transport in A6 cells and that this effect may be mediated through a rise in both intracellular calcium and cellular cAMP.
Rodriguez-Commes
J
J
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Forrest
J N
JN
Lopez
R
R
Gasalla-Herraiz
J
J
Isales
C M
CM
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D016048:Dideoxyadenosine / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D014982:Xenopus laevis
D000067956:Adenylyl Cyclase Inhibitors; D010281:Parathyroid Hormone; D005576:Colforsin; D000001:Calcimycin; D016048:Dideoxyadenosine; D009568:Nitrendipine; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium