Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of central nervous system dysfunction in uremia are multifactorial and only partially characterized. Studies using sealed presynaptic nerve terminals (synaptosomes) for in vitro ion transport and metabolism of neurotransmitter in chronic renal failure (CRF) neuronal cell culture and in vivo brain structure microdialysis generated significant new information. An increase in total calcium content of the cerebral cortex accompanied by increased levels of cytosolic calcium ([Ca(2+)]i) in synaptosomes are common findings in rats with CRF. Mechanisms leading to the increase in [Ca(2+)]i include increased calcium uptake mediated by parathyroid hormone and decreased activity of Na(+),K(+)-adenosine triphosphatase (ATPase) and Ca(2+)-ATPase of synaptosomes in CRF rats. Moreover, these synaptosomes respond inappropriately to depolarization, which can impair neurotransmitter metabolism. Brain gamma-aminobutyric acid content, norepinephrine, and acetylcholine release uptake and degradation are affected by uremia. These may lead to certain somatic, behavioral, and motor dysfunctions in uremia. Many derangements of the central nervous system in uremia appear to be mediated by secondary hyperparathyroidism of CRF because parathyroidectomy of animals with CRF prevented the increase in basal levels of [Ca(2+)]i and derangements in neurotransmitter metabolism. The role of other neurotoxins, such as guanidinosuccinic acid, are also reviewed.
 ...
PMID:Central nervous dysfunction in uremia. 1157 37

19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD(2) or 1,25(OH)(2)D(3). Calcium absorption increased from 16.5% +/- 7.8% in vehicle-treated rats to 27.5% +/- 7.2% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 21.6% +/- 3.9%, 26.2% +/- 5.5%, and 27.4% +/- 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). Similar results were obtained for phosphate absorption, with an increase from 28.2% +/- 5.5% in vehicle-treated rats to 40.2% +/- 4.7% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 32.9% +/- 2.2%, 36.2% +/- 4.5%, and 36.8% +/- 3.8% in rats given 10, 50, and 100 ng/day 19-norD(2), respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.
 ...
PMID:Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport. 1203 88