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Biomedical subjects

M Levi

Publications and source records attributed to M Levi.

At least 145 records · Page 8Linked to original sources
PubMed1999

Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation.

BACKGROUND: We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current (ICa) and that this is the principal mechanism of the action potential duration and refractoriness changes that characterize tachycardia-induced atrial remodeling. The present study was designed to determine whether atrial tachycardia alters biochemical indices of the number of L-type Ca2+ channels and/or of the number and binding affinity of beta-adrenergic receptors. METHODS: In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridine receptors were determined with the use of 3H-nitrendipine and that of beta-adrenergic receptors with 125I-iodocyanopindolol. Results were obtained with preparations from dogs paced at 400/min for 1 (P1, n = 20), 7 (P7, n = 9), and 42 (P42, n = 9) days, and compared with observations in sham-operated controls (P0, n = 14). RESULTS: Pacing reduced the Bmax of dihydropyridine receptors, from 157 +/- 18 fmol/mg (P0) to 116 +/- 9 fmol/mg (P1, P < 0.05), 100 +/- 14 fmol/mg (P7, P < 0.05) and 94 +/- 9 fmol/mg (P42, P < 0.01). The affinity of dihydropyridine receptors was unchanged, with the Kd averaging 711 +/- 102 pM. 656 +/- 74 pM, 633 +/- 155 pM and 585 +/- 92 pM in P0, P1, P7 and P42 dogs. Neither Bmax nor Kd of beta-adrenergic receptors was altered by rapid pacing. Values of Bmax of dihydropyridine receptors correlated with atrial ICa current density (r2 = 0.95) and ERP (r2 = 0.99). CONCLUSIONS: Rapid atrial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of beta-adrenergic receptors. The reductions in ICa that play an important role in the atrial electrical remodeling by which 'AF begets AF' appear to be due at least in part to a decrease in the number of L-type Ca2+ channels in cardiac cell membranes.

Adrenergic beta-Antagonists↗
PubMed1999

Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects.

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence of tcu-PA/T in human subjects with a varying degree of hypercoagulability. tcu-PA/T was assessed in the plasma of patients with disseminated intravascular coagulation (DIC), endotoxin-treated volunteers, patients with unstable angina pectoris, and patients selected for hip replacement. Relationships between tcu-PA/T and several markers reflecting thrombin generation were examined. tcu-PA/T was observed only in the plasma of patients with DIC and was associated with all thrombin markers and with scu-PA and urokinase antigen. Prothrombin fragment 1 + 2 and urokinase antigen were independent predictors of tcu-PA/T. The fact that tcu-PA/T could not be detected in the other three groups was explained by a lower extent of thrombin generation, a greater inhibition of thrombin by antithrombin, or less available urokinase antigen in these groups. The contribution of scu-PA to total urokinase antigen was decreased in the patients with DIC because of inactivation by thrombin, which may be an additional explanation for the inadequate fibrinolysis observed in these patients. These findings show that scu-PA can be inactivated in the circulation under severe pathophysiologic circumstances and that the process of inactivation depends not only on the generation of thrombin but also on the control of thrombin activity by its inhibitor antithrombin.

Angina Pectoris↗
PubMed1999

The role of B-cells in experimental myasthenia gravis in mice.

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused by auto-antibodies against the nicotinic acetylcholine receptor (AChR) at the postsynaptic membrane. To evaluate the extent to which the humoral immune response against AChR operates in the pathogenesis of EAMG, we immunized B-cell knockout (microMT) and wild type C57BL/6 mice with AChR in complete Freund's adjuvant. The ability of AChR-primed lymph node cells to proliferate and secrete IFN-gamma in response to AChR and its dominant peptide alpha 146-162 were intact in microMT as in wild type mice. Similar levels of mRNA for IFN-gamma, IL-4 and IL-10 in AChR-reactive lymph node cells were detected in microMT and wild type mice. However, microMT mice had no detectable anti-AChR antibodies and never developed clinical EAMG. We conclude that B-cells are critically required for the genesis of clinical EAMG, but not for AChR-specific T-cell priming.

Animals↗
PubMed1999

The use of peptides from glycoproteins G-2 and D-1 for detecting herpes simplex virus type 2 and type-common antibodies.

BACKGROUND: identification and discrimination of latent herpes simplex virus (HSV) infection relies on antibody identification. The inclusion of synthetic peptides with HSV glycoproteins provides means for stable and discriminatory assays for population studies. OBJECTIVE: to determine whether virus-specific synthetic peptides might identify HSV type 2 (HSV-2) antibodies in the presence of the cross-reactive and more common HSV type 1 (HSV-1) antibodies. STUDY DESIGN: the capacity of synthetic peptides as HSV antigens was analyzed in enzyme immunoassay (EIA) using well characterized human serum cohorts. The HSV peptide assays were evaluated in comparison with two commercial HSV-2 assays. RESULTS: a combination of two C-terminal HSV-1 glycoprotein D (gD-1) peptides detected type-common HSV immunoglobulin G (IgG) with high sensitivity (95%) and specificity (93%). Peptides derived from the C-terminus of HSV-2 glycoprotein G (gG-2) had a high HSV-2 type-specificity. Inclusion of both gD-1 and gG-2 peptides gave a sensitivity for human anti-HSV-2 IgG that was similar to that of assays including different amounts of native gG-2. With western blotting as a standard, the sensitivity of the peptide assay ranged between 86% for HSV-2 seropositive persons and 61% for HSV-2 seroconverters. Addition of a small amount of native gG-2 to the peptide assay tended to increase the specificity. CONCLUSION: HSV gG and gD peptides show promise as type-specific and type-common HSV antigens. These peptides are more stable and reproducibly prepared than native or recombinant glycoproteins and may be considered for inclusion in future HSV serodiagnostic assays.

Adolescent↗
PubMed1999

Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure.

Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.

Animals↗
PubMed1999

Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits.

Severe thrombocytopenia frequently occurs in patients receiving chemotherapy and in patients with autoimmune disorders. Thrombocytopenia is associated with bleeding, which may be serious and life threatening. Current treatment strategies for thrombocytopenia may require transfusion of allogeneic platelets, which is associated with serious drawbacks. These include the occurrence of anti-platelet antibodies, which may result in refractoriness to further platelet transfusions, and the potential risk of transfer of blood-borne diseases. Therefore, we have recently developed a platelet substitute product (Synthocytes), which is composed of human albumin microcapsules with fibrinogen immobilized on their surface. Here we show that the intravenous administration of these microcapsules not only corrects the prolonged bleeding time in rabbits rendered thrombocytopenic either by anti-platelet antibodies or by chemotherapy, but also reduces bleeding from surgical wounds inflicted in the abdominal skin and musculature. No potential systemic prothrombotic effect of the microcapsules was observed in a model of rabbit venous thrombosis. As for the mechanism of action, experiments with normal and thrombocytopenic human blood in an endothelial cell matrix-coated perfusion chamber demonstrated an interaction between the fibrinogen-coated albumin microcapsules and native platelets. It was shown that the fibrinogen-coated albumin microcapsules could facilitate platelet adhesion to endothelial cell matrix and correct the impaired formation of platelet aggregates in relatively platelet-poor blood. This study indicates that fibrinogen-coated albumin microcapsules can act to improve primary hemostasis under thrombocytopenic conditions and may eventually be a promising agent for prophylaxis and treatment of bleeding in patients with severe thrombocytopenia.

Albumins↗
PubMed1999

Dendritic cell-derived nitric oxide is involved in IL-4-induced suppression of experimental allergic encephalomyelitis (EAE) in Lewis rats.

Cytokines play a crucial role in initiating and perpetuating EAE, an animal model of multiple sclerosis (MS). A low dose of IL-4, administered by the nasal route over 5 days (100 ng/rat per day) prior to immunization, improved clinical scores of EAE induced in Lewis rats with myelin basic protein (MBP) peptide 68-86 (MBP 68-86). We examined whether dendritic cells (DC) may have contributed to the amelioration of the disease process. These professional antigen-presenting cells (APC) not only activate T cells, but also tolerize T cells to antigens, thereby minimizing autoimmune reactions. We found that IL-4 administration enhanced proliferation of DC. In comparison with DC of PBS-treated rats, DC from IL-4-treated rats secreted high levels of interferon-gamma (IFN-gamma) and IL-10. Nitric oxide (NO) production by DC was also strongly augmented in IL-4-treated rats. In vitro studies showed that IL-4 stimulated DC expansion and that IFN-gamma enhanced NO production by DC. DC-derived NO promoted apoptosis of autoreactive T cells. These results indicate that nasal administration of IL-4 promotes activation of DC and induces production of IFN-gamma and IL-10 by DC. IL-10 suppresses antigen presentation by DC, while IFN-gamma induces NO production by DC which leads to apoptosis in autoreactive T cells. Such a DC-derived negative feedback loop might contribute to the clinical improvement observed in EAE.

Animals↗
PubMed1999

Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6.

Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as experimental model for human immune-demyelinating neurophathies, especially the Guillain-Barré syndrome. In this study, we examined the effect of recombinant rat interleukin-6 (rrIL-6) on chronic EAN in Lewis rats induced by immunization with P2 peptide 57-81 and Freund's complete adjuvant (FCA). Nasal administration of rat rIL-6 (1 microg/rat/day) beginning in the initial phase of EAN as a therapeutic agent, decreased the severity and the duration of clinical EAN. Low-grade inflammation and suppression of regional demyelination within the sciatic nerves were seen in rrIL-6-treated rats. Hyporesponsiveness of lymph node T cells, down-regulation of serum tumour necrosis factor-alpha (TNF-alpha) and increased levels of P2-specific immunoglobulin G1 (IgG1) antibodies document that nasal administration of rrIL-6 was effective systemically. However, because of the non-specific nature of the treatment and multiple effects of IL-6, more experience and great caution are needed, before nasal administration of IL-6 can be considered as a treatment of human autoimmune demyelinating neurophathies.

Administration, Intranasal↗
PubMed1999

Chronic K depletion inhibits renal brush border membrane Na/sulfate cotransport.

BACKGROUND: The purpose of this study was to determine if dietary potassium (K) deficiency regulates renal proximal tubular sodium gradient-dependent sulfate transport (Na/Si cotransport) in the rat and, furthermore, determine if the regulation takes place at the level of the recently cloned Na/Si cotransport system (NaSi-1). Methods and Results. Rats treated chronically (seven days) with a K-deficient diet had a significant decrease in serum Si levels and an increase in fractional excretion of ultrafilterable Si, which paralleled a significant decrease in brush border membrane (BBM) Na/Si cotransport activity. The decrease in BBM Na/Si cotransport activity was associated with decreases in BBM NaSi-1 protein and renal cortical NaSi-1 mRNA abundance. In addition, in Xenopus oocytes injected with mRNA from kidney cortex slices of K-deficient rats, there was a significant reduction in the induced Na/Si cotransport, whereas there was no alteration in l-leucine uptake, suggesting that in K-deficient rats, there is a specific decrease in functional mRNA encoding the NaSi-1 mRNA. CONCLUSION: These findings indicate that chronic K deficiency leads to a reduction in serum Si levels and an increase fractional excretion of Si, and reduces Si reabsorption by down-regulating the expression of the proximal tubular Na/Si-1 cotransporter protein and mRNA.

Animals↗
PubMed1999

Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees.

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.

Animals↗
PubMed1999

Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions.

Only two virus-neutralizing peptide microantibodies (MicroAbs) have been described and little is known about their mode of action. This report concerns a 17 amino acid cyclized MicroAb, derived from the third complementarity-determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same minimum epitope in the V3 loop of the gp120 envelope protein of human immunodeficiency virus type 1 (HIV-1) as the MAb. The MicroAb was able to bind to and neutralize free virus particles. It was up to 5-fold more efficient in mass terms than F58 IgG and its neutralization rate on a molar basis was only 32-fold lower. The mechanism of neutralization of the MicroAb was also investigated. A high level of neutralization (99%) occurred without any significant decrease in attachment of virus to target C8166 cells. Neutralized virus attached to CD4, the HIV-1 primary receptor. Fusion of virions to cells was partially inhibited by the MicroAb, whereas F58 IgG has been shown to inhibit fusion significantly. Thus, neutralization by the MicroAb appears to be mediated, at least in part, by inhibition of fusion. Control peptides, in which the tyrosine at position 5 or 6 was deleted or changed to phenylalanine, showed no antiviral activity, attesting to the specificity of interaction of the MicroAb with the virion. It therefore appears that the MicroAb acts like an immunoglobulin. The data also show that the MicroAb/MAb F58 epitope on the V3 loop is not involved in attachment of virus to CD4 but is required for subsequent events in early infection.

Amino Acid Sequence↗
PubMed1999

Divergent roles of tumor necrosis factor and platelet-activating factor in endotoxin-induced release of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta in chimpanzees.

A platelet-activating factor receptor antagonist reduced the release of macrophage inflammatory protein 1beta (MIP-1beta) during endotoxemia in chimpanzees but did not influence the secretion of monocyte chemoattractant protein 1 (MCP-1). Anti-tumor necrosis factor alpha monoclonal antibody completely prevented MCP-1 release and simultaneously enhanced the secretion of MIP-1beta. Levels of MIP-1beta and MCP-1 release were differentially regulated during endotoxemia.

Animals↗
PubMed1999

Metabolic acidosis regulates rat renal Na-Si cotransport activity.

Recently, we cloned a cDNA (NaSi-1) localized to rat renal proximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate (Si) transport protein (Na-Si cotransporter). The purpose of the present study was to determine the effect of metabolic acidosis (MA) on Na-Si cotransport activity and NaSi-1 protein and mRNA expression. In rats with MA for 24 h (but not 6 or 12 h), there was a significant increase in the fractional excretion of Si, which was associated with a 2.4-fold decrease in BBM Na-Si cotransport activity. The decrease in Na-Si cotransport correlated with a 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2.2-fold decrease in cortical NaSi-1 mRNA abundance. The inhibitory effect of MA on BBM Na-Si cotransport was also sustained in rats with chronic (10 days) MA. In addition, in Xenopus laevis oocytes injected with mRNA from kidney cortex, there was a significant reduction in the induced Na-Si cotransport in rats with MA compared with control rats, suggesting that MA causes a decrease in the abundance of functional mRNA encoding the NaSi-1 cotransporter. These findings indicate that MA reduces Si reabsorption by causing decreases in BBM Na-Si cotransport activity and that decreases in the expression of NaSi-1 protein and mRNA abundance, at least in part, play an important role in the inhibition of Na-Si cotransport activity during MA.

Acidosis↗
PubMed1999

Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats.

In the present study, we determined the effect of epidermal growth factor (EGF; 10 microgram/100 g body wt) on sodium gradient-dependent phosphate transport (Na-Pi cotransport) regulation in suckling (12-day-old) and weaned (24-day-old) rats. Weaned rats had higher proximal tubular brush border membrane vesicle (BBMV) Na-Pi cotransport activity (232 +/- 16 in weaned vs. 130 +/- 9 pmol. 10 s-1. mg protein-1 in suckling rats, P < 0.05). Chronic treatment with EGF induced inhibition of BBMV Na-Pi cotransport in both suckling (130 +/- 9 vs. 104 +/- 7 pmol. 10 s-1. mg protein-1, P < 0. 05) and weaned rats (232 +/- 16 vs. 145 +/- 9 pmol. 10 s-1. mg protein-1, P < 0.005). The inhibitory effect was selective for Na-Pi cotransport as there was no inhibition of Na-glucose cotransport. Weaned rats had a higher abundance of BBMV NaPi-2 protein than suckling rats (increase of 54%, P < 0.001) and a twofold increase in NaPi-2 mRNA. The EGF-induced inhibition of Na-Pi transport was paralleled by decreases in NaPi-2 protein abundance in both weaned (decrease of 26%, P < 0.01) and suckling (decrease of 27%, P < 0.01) animals. In contrast, there were no changes in NaPi-2 mRNA abundance. We conclude that proximal tubule BBMV Na-Pi cotransport activity, NaPi-2 protein abundance, and NaPi-2 mRNA abundance are higher in weaned than in suckling rats. EGF inhibits Na-Pi cotransport activity in BBMV isolated from suckling and weaned rats, and this inhibition is mediated via a decrease in NaPi-2 protein abundance, in the absence of a change in NaPi-2 mRNA.

Animals↗
PubMed1999

Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients.

Cyclosporin A (CsA) has been implicated as one of the factors contributing to the high cardiovascular morbidity and mortality after renal transplantation. This may be mediated by either a high prevalence of conventional risk factors for atherosclerosis, such as hypertension, hypercholesterolemia, and diabetes mellitus, or by impairment of the fibrinolytic activity evoked by CsA, possibly through interference with prostanoid metabolism. We therefore assessed the impact of conversion of CsA to azathioprine immunosuppressive treatment on parameters of fibrinolytic activity and plasma concentration of the prostanoids prostaglandin E2 and thromboxane B2 in 18 stable renal transplant recipients. During CsA, mean arterial pressure and serum creatinine were significantly higher than during azathioprine (116+/-15 mm Hg versus 106+/-13 mm Hg, P=0.0003; and 147+/-34 micromol/L versus 127+/-35 micromol/L, P=0.002; mean+/-SD). On conversion, the plasma tissue plasminogen activator activity increased from 1.2 (1.1 to 1.7; median, 95% CI) to 1.8 (1.6 to 2.0) IU/mL (P=0.011), without a significant change of the plasminogen activator antigen concentration. This was associated with a substantial decrease in plasminogen activator inhibitor-1 activity from 10.4 (8.5 to 16.7) to 6.4 (5.6 to 9.2) IU/mL (P=0.009). Furthermore, plasma levels of prostaglandin E2 and thromboxane B2 markedly decreased (from 9.7 [7.4 to 12.9] to 4.6 [4.3 to 8.1] pg/mL, P=0.0006; and from 106.1 [91.7 to 214.2] to 70.2 [50.3 to 85.6] pg/mL, P=0.002, respectively). During CsA, but not azathioprine, plasma tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels correlated significantly with prostaglandin E2 (r=0.53, P=0.02; and r=0.60, P=0.008, respectively), and thromboxane B2 (r=0.75, P=0.0001; and r=0.77, P=0.0001, respectively) levels. In conclusion, CsA induced substantial impairment of fibrinolytic activity, which recovered after conversion to azathioprine. The impaired fibrinolysis observed during CsA treatment may be caused by modulation of eicosanoid production or metabolism in vascular endothelial cells and possibly contributes to the high incidence of cardiovascular disease after kidney transplantation.

Adult↗
PubMed1999

Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement.

Renal proximal tubule cells express in their apical brush border membrane (BBM) a Na/P(i) cotransporter type IIa that is rapidly downregulated in response to parathyroid hormone (PTH). We used the rat renal Na/P(i) cotransporter type IIa (NaPi-2) as an in vivo model to assess early cellular events in the rapid downregulation of this transporter. When rats were treated with PTH for 15 minutes, NaPi-2 abundance in the BBM was decreased. In parallel, transporter accumulated in intracellular vesicles. Concomitantly, microtubules (MTs) were found to form dense bundles of apical-to-basal orientation. After 60 minutes of PTH action, the cells were vastly depleted of NaPi-2, whereas their microtubular cytoskeleton had returned to its normal appearance. Prevention of MT rearrangement by taxol resulted in accumulation of NaPi-2 in the subapical cell portion after 15 minutes and a strong delay in depletion of intracellular transporter after 60 minutes of PTH action. Furthermore, the subapical accumulation of NaPi-2 was associated with the expansion of dense apical tubules of the subapical endocytic apparatus (SEA). Depolymerization of MTs by colchicine likewise caused a retardation of intracellular NaPi-2 depletion. These results suggest that NaPi-2 is downregulated in response to PTH through a rapid endocytic process in 2 separate steps: (a) internalization of the transporter into the SEA, and (b) its delivery to degradative organelles by a trafficking mechanism whose efficiency depends on a taxol-sensitive rearrangement of MTs.

Animals↗
PubMed1999

Role of thyroid hormone in regulation of renal phosphate transport in young and aged rats.

In the present study, we have examined the cellular mechanisms mediating the regulation of renal proximal tubular sodium-coupled inorganic phosphate (Na/Pi) transport by thyroid hormone (T3) in young and aged rats. Young hypothyroid rats showed a marked decrease in Na/Pi cotransport activity, which was associated with parallel decreases in type II Na/Pi cotransporter (NaPi-2) protein and messenger RNA (mRNA) abundance. In contrast, administration of long-term physiological and supraphysiological doses of T3 resulted in significant increases in Na/Pi cotransport activity, protein, and mRNA levels. Nuclear run-on experiments indicated that thyroid hormone regulates NaPi-2 mRNA levels by a transcriptional mechanism. In aged rats, although there were no changes in T3 serum levels (when compared with young animals), there were significant decreases in serum Pi concentration, renal Na/Pi cotransport activity, and NaPi-2 protein and mRNA abundance. These effects were mediated, at least in part, by a reduction in the transcriptional rate of the NaPi-2 gene, probably caused by, among other factors, a smaller response to the stimulatory action of T3. Compared with young rats, the old rats exhibited less sensitivity of the Na/Pi cotransporter to thyroid hormone, with-decreased effects in both hypothyroid (inhibitory) and hyperthyroid (stimulatory) animals.

Absorption↗