Parathyroid hormone mediates changes in calcium transport in uremic rat brain synaptosomes.
In previous studies, we showed that Ca2+ transport by both Na+ gradient-stimulated Ca2+ uptake and ATP-stimulated Ca2+ uptake was increased in synaptosomes from uremic rat brain. The possible role of parathyroid hormone (PTH) in this observation was investigated by performing Ca2+ transport studies in synaptosomes by these two mechanisms. Studies were performed in vesicles from rats that were either normal, uremic, uremic parathyroidectomized (PTX-U), or uremic parathyroidectomized but treated with PTH. In uremic rats, transport by both Na+ gradient-stimulated Ca2+ uptake and ATP-stimulated Ca2+ uptake was increased by 30 and 47%, respectively, whereas uptake was returned to base line in synaptosomes from PTX-U rats. Additionally, the administration of PTH to PTX-U rats resulted in a significant increase (P less than 0.001) of 36 and 41%, respectively, above the values observed in PTX-U rats. To determine whether the increased accumulation of Ca2+ in synaptosomes in uremia was a result of PTH alone and/or to the uremic environment, we next performed uptake studies in synaptosomes that were isolated from nonuremic rats that were either normal, parathyroidectomized (PTX) or PTX but treated with 2.8-100 micrograms PTH. By both transport mechanisms, uptake was significantly (P less than 0.01) decreased from normal by 27% in the PTX group, and either 2.8 or 110 micrograms PTH resulted in a significant increase in transport to base line by Na+-gradient stimulated Ca2+ uptake. However, Ca2+ accumulation by ATP-stimulated Ca2+ uptake was significantly increased to base line only with 100 micrograms PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Fraser
C L
CL
Department of Medicine, Veterans Administration Medical Center, San Francisco, California.
Sarnacki
P
P
D000818:Animals; D001806:Blood Urea Nitrogen; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D014511:Uremia / Q000378:metabolism*
D010281:Parathyroid Hormone; D002118:Calcium