The mechanism of parathyroid hormone action on calcium reabsorption by the distal tubule.
PTH increases calcium reabsorption exclusively in the distal nephron. Two mechanisms of Ca++ transport through the basolateral membrane (BLM) have been described: the ATP-dependent and the sodium gradient-dependent transport. In the present study, we investigated the effect of PTH and (Bu)2cAMP on these two mechanisms. We recently reported, using 100 microM Ca++ as the substrate, that whereas the ATP-dependent system was present in the proximal and distal tubule (DCT), the Na+/Ca++ exchanger was located only in the DCT. Using 2 microM Ca++ as the substrate, the Na+/Ca++ exchanger was again found to be present only in the DCT. Incubation of DCT suspension with 10(-8) M bovine PTH (1-34) resulted in a significant increase in the Na(+)-dependent Ca++ uptake by the corresponding BLM vesicles. This effect was dose dependent. The half-maximal stimulation was obtained with 1 X 10(-8) M PTH. At this concentration, PTH increased the maximum velocity (Vmax) from 0.34 +/- 0.06 t 0.54 +/- 0.02 nmol/mg/10 s (P less than 0.05) without influencing the Michaelis-Menten constant (Kms). Incubation of DCT suspensions with (Bu)2cAMP mimicked this effect. The dose-response curve showed a peak action at 1 mM (Bu)2cAMP. In contrast, neither (Bu)2cAMP nor PTH influenced the ATP-dependent Ca++ transport through BLM from proximal tubule nor DCT. It is proposed that PTH influences Ca++ reabsorption by the DCT because the target molecule, the Na+/Ca++ exchanger, is located exclusively at this site.
Bouhtiauy
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I
Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
Lajeunesse
D
D
Brunette
M G
MG
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011817:Rabbits; D019831:Sodium-Calcium Exchanger; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D019831:Sodium-Calcium Exchanger; D003994:Bucladesine; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium