Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the possible existence and nature of Ca2+ transport in frog skin using 45Ca fluxes and short-circuiting technique. Following the addition to full-thickness frog skin (FTFS) of 8-[p-chlorophenylthio]cAMP (8-CPT-cAMP), forskolin, or 1-methyl-3-isobutylxanthine, the secretory Ca2+ flux increased severalfold, inducing net Ca2+ secretion. The absorptive flux was unchanged. Isoproterenol (10(-6)M) reproduced the effects of cAMP on Ca2+ secretion (-3.76 +/- 0.80 nmol X cm-2 X h-1 vs. +0.04 +/- 0.05 in control) while vasopressin and parathyroid hormone did not alter Ca2+ fluxes. Because FTFS contains subepidermal glands capable of Cl- secretion in response to beta-adrenergic stimulation, split-thickness frog skin (STFS) consisting of the gland-free Na-absorbing surface epithelium was used to localize the anatomic site of Ca2+ secretion. In STFS, addition of 8-CPT-cAMP or isoproterenol failed to induce Ca2+ secretion, suggesting that this transport in FTFS is localized in skin glands. Additional studies explored the relationship between Ca2+ and Cl- transport in FTFS. Furosemide prevented the stimulation of both Ca2+ and Cl- secretion. Removal of Cl- from the bathing medium abolished Ca2+ secretion. Thus, FTFS exhibits a beta-adrenergic, cAMP-stimulated net Ca2+ secretion that is Cl- dependent. As this effect is not observed in STFS, the pathway of Ca2+ secretion in frog skin is probably localized in the subepidermal glandular epithelium in association with Cl- secretion. Frog skin glands may represent a useful model for the study of Ca2+ transport in Cl--transporting epithelia.
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PMID:cAMP- and beta-adrenergic-stimulated chloride-dependent Ca2+ secretion in frog skin. 241 6

To characterize the Ca2+ transport process across the apical membrane of the rabbit connecting tubule (CNT), we examined the effects of luminal pressure on parathyroid hormone (PTH)-dependent apical Ca2+ transport in this segment perfused in vitro. An increase of perfusion pressure (0.2 to 1.2 KPa) caused cytoplasmic free Ca2+ concentration ([Ca2+]i) to increase by 42 +/- 11 nM in Fura-2 loaded perfused CNT. The response was accentuated when 10 nM PTH was added to the bath (101 +/- 30 nM, n = 6). Addition of 0.1 mM chlorphenylthio-cAMP (CPT-cAMP) to the bath also augmented the [Ca2+]i response to pressure from 36 +/- 16 to 84 +/- 26 nM (n = 3). Under steady perfusion pressure at 1.2 KPa, PTH (10 nM) increased [Ca2+]i by 31 +/- 7 nM (n = 5), whereas it did only slightly by 6 +/- 2 nM (n = 12) at 0.2 KPa. The pressure-dependent increase of [Ca2+]i was abolished by removing luminal Ca2+ (n = 3), and was not affected by 0.1 and 10 microM nicardipine (n = 4) in the presence of 10 nM PTH. Cell-attached patch clamp studies on the apical membrane of everted CNT with pipettes filled with either 200 mM CaCl2 or 140 mM NaCl revealed channel activities with conductances of 42 +/- 2 pS (n = 4) or 173 +/- 7 pS (n = 5), respectively. An application of negative pressure (-4.9 KPa) to the patch pipette augmented its mean number of open channels (NPo) from 0.005 +/- 0.001 to 0.022 +/- 0.005 in the Ca(2+)-filled pipette, and was further accelerated to 0.085 +/- 0.014 (n = 3) by 0.1 mM CPT-cAMP. In the Na(+)-filled pipette, similar results were obtained (n = 3), and CPT-cAMP did not activate the stretch-activated channel in the absence of negative pressure (n = 3). These results suggest that a stretch-activated nonselective cation channel exists in the apical membrane of the CNT and that it is activated by PTH in the presence of hydrostatic pressure, allowing entry of Ca2+ transport from the apical membrane.
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PMID:Pressure- and parathyroid-hormone-dependent Ca2+ transport in rabbit connecting tubule: role of the stretch-activated nonselective cation channel. 793 46

A 14-year-old girl, having mental and growth retardation with end stage renal disease, was affected by a stroke-like attack. The attack was associated with transient low density areas at both sides of the parietal portion on head CT. Lactic acidosis, hypertrophic cardiomyopathy, angina pectoris-like attacks, hypertension and hyperparathyroidism were also observed and they were supposedly due to mitochondrial cytopathy. No morphological or biochemical abnormalities were found on the mitochondrial respiratory chain. However, muscle carnitine palmitoyltransferase (CPT) activity was significantly low, which was restored to a normal level after hyperparathyroidism was controlled by alphacalcidol administration. Furthermore, we also found two more chronic renal failure patients with secondary hyperparathyroidism, as well as the primary hyperparathyroidism patient showing markedly low muscle CPT activity. These findings suggest the possible contribution of parathyroid hormone to lipid metabolism in skeletal muscle and to the myopathic manifestations often seen in hyperparathyroidism.
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PMID:Secondary carnitine palmitoyltransferase deficiency in chronic renal failure and secondary hyperparathyroidism. 872 13

Etelcalcetide is a novel calcimimetic in development for the treatment of secondary hyperparathyroidism (SHPT). A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed relating etelcalcetide exposures to markers of efficacy (parathyroid hormone [PTH]) and safety (calcium) using data from three clinical studies. The semimechanistic model was developed that included allosteric activation pharmacology and understanding of calcium homeostasis. The temporal profiles for all biomarkers were well described by the model. The cooperativity constant was 4.94, confirming allosteric activation mechanism. Subjects with more severe disease (higher PTH baseline) were predicted to experience less pronounced reduction in PTH (percentage change from baseline), but more reduction in calcium (Ca; percentage change from baseline). There was no evidence that dose adjustment by any covariate was needed. Model-based simulations provided quantitative support to several elements of dosing, such as starting dose, monitoring, and titration timing for registration trials.
CPT Pharmacometrics Syst Pharmacol 2016 09
PMID:Population Pharmacokinetics and Pharmacodynamics of the Calcimimetic Etelcalcetide in Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Hemodialysis. 2763 83