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Biomedical subjects

M Smogorzewski

Publications and source records attributed to M Smogorzewski.

At least 37 records · Page 2Linked to original sources
PubMed1997

Role of elevated cytosolic calcium in the pathogenesis of complications in diabetes mellitus.

Both type I and type II diabetes mellitus are associated with derangements in the regulation of intracellular calcium. Hyperglycemia causes an acute rise in cytosolic calcium ([Ca2+]i) due to increased calcium influx and in certain cells to mobilization of intracellular calcium stores as well. The increase in calcium entry is secondary to the activation of calcium channels inhibitable by verapamil, nifedipine, or amlodipine. The stimulation of these calcium channels is mediated by the activation of G protein(s), leading to stimulation of various cellular pathways. Chronic hyperglycemia is also associated with decreased calcium exit from cells. The combination of increased calcium influx and decreased calcium efflux leads to sustained elevation in basal levels of [Ca2+]i. The latter abnormality may adversely affect cell function. Treatment of diabetic animals with calcium channel blockers normalizes cell [Ca2+]i and prevents and/or reverses the derangements in cellular function.

Animals↗
PubMed1996

Abnormalities in hepatic lipase in chronic renal failure: role of excess parathyroid hormone.

Post-heparin hepatic lipase activity is reduced in chronic renal failure (CRF). This could be due to reduced synthesis, decreased activity, and/or impaired secretion of the enzyme. Further, the factor(s) responsible for such derangements are not elucidated. We examined hepatic lipase metabolism in normal, 6-wk-old CRF rats, CRF-PTX (parathyroidectomized) rats, and CRF and normal rats treated with verapamil (CRF-V, normal-V) using liver homogenate, hepatic cell culture for 8 h, and in vitro liver perfusion. The Vmax of hepatic lipase in liver homogenate was significantly (P < 0.01) reduced and the Km was significantly (P < 0.01) increased in CRF rats, but the values were normal in CRF-PTX, CRF-V, and normal-V rats. Culture of hepatic cells for 8 h was associated with an increase in hepatic lipase activity but the increment in CRF rats was significantly (P < 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats. Both parathyroid hormone (PTH)-(1-84) and 1-34 inhibited the production of hepatic lipase in cultured cells from normal, CRF-PTX, CRF-V, and normal-V rats. The expression of the mRNA of the hepatic lipase was significantly reduced in CRF animals with the ratio between it and that of house keeping gene G3DPH being 15 +/-3% compared to 40 +/- 1.3% in normal, 44+/-2.9% CRF-PTX, 44 +/- 5.4% in CRF-V, and 39 +/- 3.9% in normal-V rats. Infusion of heparin to the in vitro hepatic perfusion system increased the activity of hepatic lipase in the effluent in all groups of rat except in CRF animals. Infusion of PTH-(1-34) in dose of 10(-6) M into the liver perfusion system inhibited the increase in post-heparin hepatic lipase activity. The data show that in CRF (a) the mRNA of hepatic lipase is downregulated, and hepatic lipase production, activity and release are impaired, (b) that this is due to the state of secondary hyperparathyroidism of CRF since both acute and chronic excess of PTH were associated with these abnormalities, (c) and that prevention of excess PTH by PTX of CRF rats or blocking the effect of PTH by treatment with verapamil corrected the derangement in hepatic lipase metabolism.

Animals↗
PubMed1996

Elevation of cytosolic calcium of rat cardiac myocytes in phosphate depletion.

Phosphate depletion is associated with a rise in cytosolic calcium ([Ca2+]i) of cells and such a derangement is responsible in major part for organ dysfunction in phosphate depletion (PD). Cardiac function is impaired in PD, and it is possible that PD is also associated with rise in [Ca2+]i of cardiac myocytes. The present study examined the effect of PD on [Ca2+]i of cardiac myocytes and explored the mechanisms that may lead to the rise in their [Ca2+]i. The [Ca2+]i of cardiac myocytes began to rise and ATP content began to fall at the third week of PD. After six weeks of PD, the values of [Ca2+]i were significantly higher (P < 0.01) and those of ATP content were significantly lower (P < 0.01) than in control (PW) rats. The Vmax of Ca2(+)-ATPase and Na+,K(+)-ATPase as well as the Na(+)-Ca2+ exchange were significantly lower (P < 0.01) in PD than in PW animals. The data of the present study are consistent with the notion that the rise in [Ca2+]i of cardiac myocytes of PD rats is due to a decrease in calcium efflux out of them.

Adenosine Triphosphate↗
PubMed1996

Nifedipine reverses the abnormalities in [Ca2+]i and proliferation of B cells from dialysis patients.

Both animals and patients with chronic renal failure have impaired B cell function due, in part, to elevated levels of cytosolic calcium ([Ca2+]i). Treatment of HD patients with nifedipine has normalized [Ca2+]i of their polymorphonuclear leukocytes (PMNL) and caused marked improvement in the phagocytic property of the PMNL. This observation may have important clinical implications if this drug exerts a similar effect on other cells such as B cells. We examined [Ca2+]i, proliferation of B cells in response to mitogen, the magnitude of the PTH-induced inhibition of B cell proliferation, and the ATP content of mononuclear cells in 11 hemodialysis patients treated with nifedipine, 12 patients without nifedipine therapy and 11 normal subjects. Serum levels of IgG was also measured in the two groups of patients. There were no significant differences in the age, duration of hemodialysis, blood levels of calcium, phosphorus or PTH (571 +/- 193 vs. 484 +/- 127 pg/ml) among the two groups of patients. The hemodialysis patients without nifedipine therapy compared to those without nifedipine treatment have significantly (P < 0.01) higher levels of [Ca2+]i (120 +/- 1.9 nM vs. 94 +/- 2.2 nM), lower ATP content of mononuclear cells (0.45 +/- 0.06 nmol/10(6) cells vs. 0.68 +/- 0.04 nmoles/10(6) cells), impaired proliferation (5.8 +/- 0.31 x 10(3) cpm vs. 9.8 +/- 0.38 x 10(3) cpm) and smaller inhibition of B cell proliferation by PTH compared to those treated with nifedipine. The values in the patients treated with nifedipine were still modestly but significantly different than in normal subjects. The serum IgG levels of the patients without nifedipine therapy (1210 +/- 71 mg/dl) were significantly lower than those of the patients treated with nifedipine (1594 +/- 81 mg/dl). Thus, the treatment of hemodialysis patients with nifedipine produced marked and significant improvement in the metabolic and functional parameters of B cells despite no changes in blood levels of PTH. These data indicate that the calcium channel blocker, nifedipine, interferes with PTH-induced rise in [Ca2+]i of B cells of hemodialysis patients and consequently improves their metabolism and function. These observations if confirmed in other human cells may provide for a rational therapeutic approach to ameliorate the signs and symptoms of uremia.

Adenosine Triphosphate↗
PubMed1996

Pathways through which glucose induces a rise in [Ca2+]i of polymorphonuclear leukocytes of rats.

Basal levels of [Ca2+]i are elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for hyperglycemia-induced acute rise in polymorphonuclear leukocytes (PMNL), and explored whether such a rise is due to increased calcium entry into PMNL and/or to calcium release from their intracellular stores. There were dose dependent and time dependent rises in the [Ca2+]i of PMNL exposed to high concentrations of glucose. Similar effects were observed when the PMNL were exposed to high concentrations of choline chloride or mannitol. A substantial part of the rise in [Ca2+]i was inhibited when the media contained verapamil or nifedipine or when the PMNL were placed in calcium free media, and the rise in [Ca2+]i was completely abolished when the PMNL were placed in calcium free media containing ryanodine. GDP beta S or pertussis toxin almost completely prevented the glucose-induced rise in [Ca2+]i of PMNL. Rp-cAMP, H-89 or staurosporine produced significant inhibition of the rise in [Ca2+]i. High concentrations of glucose produced a dose dependent shrinkage of PMNL volume over a period of two hours. The volume of PMNL, however, was normal after 24 hours in vitro incubation studies as well as after 1, 2 and 12 days of streptozotocin-induced hyperglycemia in rats. The results are consistent with the formulation that the osmotic activity (cell shrinkage) of the high glucose concentrations activates G protein(s) which then stimulates the adenylate-cAMP-protein kinase A pathway, phospholipase C system and calcium channels. The stimulation of these cellular pathways permits both calcium influx into the PMNL as well as mobilization of calcium from their intracellular stores. Both of these events contribute to the acute rise in their [Ca2+]i. It is possible that the rise in [Ca2+]i is critical for the stimulation of the events that lead to the generation and accumulation of inorganic osmolytes to restore cell volume to normal.

Animals↗
PubMed1996

Effects of parathyroid hormone on hepatocyte pHi and Na(+)-H+ exchanger activity.

Parathyroid hormone (PTH) induces a rise in cytosolic calcium--[Ca2+]i--in many cells. A rise in [Ca2+]i activates the Na(+)-H+ antiport, but PTH inhibits the Na(+)-H+ exchanger in kidney cells. Since PTH induces a rise in [Ca2+]i of hepatocytes, we examined the effect of PTH on their Na(+)-H+ antiport and intracellular pH(pHi). PTH caused an initial activation of Na(+)-H+ exchanger, and this stimulation is amiloride sensitive. The activation of the Na(+)-H+ exchanger was followed by progressive inhibition. This inhibitory effect was dose dependent and occurred over a wide range of external sodium concentrations. PTH also caused a progressive rise in hepatocyte pHi which became apparent after the initial activation of the Na(+)-H+ antiport. This alkalinization of hepatocytes occurred when the cells were placed in sodium or potassium media. These actions of PTH were mimicked by dibutyryl cyclic AMP and 12-o-tetradecanoylphorbol-13-acetate(TPA) and were abolished by H-89 (an inhibitor of protein kinase A), staurosporine (an inhibitor of protein kinase C), and the calcium channel blockers verapamil or nifedipine. The data are consistent with the formulation that PTH, through the activation of the cAMP-protein kinase A pathway, protein kinase C, and calcium channels inhibitable by verapamil or nifedipine, induces a rise in [Ca2+]i of hepatocytes. The latter event causes an initial activation of Na(+)-H+ antiport which is followed by a rise in pHi. Also, PTH may facilitate a Ca2+/2H+ exchange across the hepatocyte membrane and causes an initial and persistent rise in pHi, since the rise in pHi occurred under conditions where Na(+)-H+ antiport is inactive (potassium media). In addition, PTH either directly or through activation of second messenger(s) leads to an increased ammonia content of hepatocytes which could maintain a high pHi. Consequently, the Na(+)-H+ antiport is inhibited in an effort to restore the pHi back to normal.

Ammonia↗
PubMed1995

Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function.

OBJECTIVE: To determine basal levels of cytosolic calcium ([Ca2+]i) and phagocytic activity in polymorphonuclear leukocytes (PMNLs) from patients with non-insulin-dependent diabetes (NIDDM). DESIGN: Prospective cohort study. SETTING: A university-county hospital. MEASUREMENTS: Cytosolic calcium levels, adenosine triphosphate (ATP) content, and phagocytosis of PMNLs from patients with NIDDM and from controls. INTERVENTION: In patients with NIDDM, we evaluated the effect of treatment with an oral hypoglycemic agent (glyburide) on [Ca2+]i levels, ATP content, and the phagocytosis of PMNLs. PATIENTS: 22 controls and 34 patients with NIDDM were examined. Fifteen patients were studied before and after 3 months of treatment with glyburide. RESULTS: Polymorphonuclear leukocytes from patients with NIDDM showed significantly elevated basal levels of [Ca2+]i (68 +/- 9.6 compared with 43 +/- 4.9 nmol/L; P < 0.01); reduced ATP content (1.30 +/- 0.58 compared with 2.35 +/- 0.45 nmol/10(6) PMNLs; P < 0.01); and impaired phagocytosis (117 +/- 21.0 compared with 145 +/- 17.4 micrograms oil/10(7) PMNLs per minute; P < 0.01) compared with controls. There was a direct and significant correlation (P < 0.01, r = 0.80) between [Ca2+]i levels in PMNLs and serum glucose levels and an inverse correlation between phagocytic ability and [Ca2+]i levels (P < 0.01; r = 0.62) as well as between phagocytic activity and fasting serum glucose levels (P < 0.01, r = 0.54) in patients with NIDDM. Glyburide therapy resulted in significant reduction in fasting serum glucose levels; in PMNLs, this treatment resulted in a significant reduction in [Ca2+]i levels, a significant increase in ATP content, and a significant improvement of phagocytosis. CONCLUSIONS: Patients with NIDDM have elevated [Ca2+]i levels in PMNLs. This abnormality is probably induced by hyperglycemia and is primarily responsible for the imparied phagocytosis seen in these patients.

Adenosine Triphosphate↗
PubMed1995

Effect of treatment of hemodialysis patients with nifedipine on metabolism and function of polymorphonuclear leukocytes.

Both animals and patients with chronic renal failure have impaired phagocytosis, which is most likely due to elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced adenosine triphosphate (ATP) content of their polymorphonuclear leukocytes (PMNLs). In animals with chronic renal failure, these derangements are prevented or reversed by their treatment with a calcium channel blocker. This observation may have important clinical implications if these drugs exert a similar effect in humans with chronic renal failure. We examined the basal levels [Ca2+]i, ATP content, and phagocytosis in PMNLs from 11 normal subjects, 18 hemodialysis patients (seven of whom had diabetes mellitus), and 18 hemodialysis patients treated with nifedipine (eight of whom had diabetes mellitus). The basal levels of the [Ca2+]i content of the PMNLs in hemodialysis patients without nifedipine therapy were significantly (P < 0.01) elevated (nondiabetic patients, 77 +/- 3.2 nmol/L; diabetic patients, 75 +/- 1.9 nmol/L) compared with normal values (42 +/- 0.9 nmol/L). Treatment with nifedipine was associated with the return of [Ca2+]i toward normal values in both the nondiabetic (51 +/- 4.5 nmol/L) and diabetic (54 +/- 2.5 nmol/L) hemodialysis patients. The ATP content of PMNLs from hemodialysis patient was significantly (P < 0.01) reduced compared with normal, and nifedipine therapy restored the ATP content to normal values. Phagocytosis was significantly (P < 0.01) impaired in hemodialysis patients (nondiabetic patients, 78 +/- 4.0 micrograms oil/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 micrograms oil/10(7) PMNLs/min). Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 +/- 2.5 micrograms oil/10(7) PMNLs/min; diabetic patients, 129 +/- 6.4 micrograms oil/10(7) PMNLs/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Parathyroid hormone stimulates the generation of inositol 1,4,5-triphosphate in brain synaptosomes.

Parathyroid hormone (PTH) increases the levels of the second messenger, inositol 1,4,5 triphosphate (I1,4,5P3) in kidney and bone cells. It has been reported the I1,4,5P3 increases calcium uptake by brain synaptosomes. Because PTH also augments calcium entry in brain synaptosomes, it is possible that PTH induces the generation of I1,4,5P3 in these structures as well. The current study examined the effect of PTH-(1-84) on myoinositol turnover in vitro in rat brain synaptosomes. PTH-(1-84) in concentration of 10(-6)mol/L significantly (P < 0.01) increased the IP3 production (35 +/- 52%). The results indicate that PTH activates the phosphoinositol turnover in brain synaptosomes and that this pathway may be involved in the PTH-induced increase in [Ca2+]i in brain synaptosomes.

Animals↗
PubMed1995

Down-regulation of PTH-PTHrP receptor of heart in CRF: role of [Ca2+]i.

The mRNA of PTH-PTHrP receptor in the kidney and liver of CRF rats is down-regulated. It is not known whether this is a generalized phenomenon and the signals that mediate such down-regulation are not evident. Excess PTH in CRF induces a rise in basal levels of cytosolic calcium ([Ca2+]i), and the high [Ca2+]i is implicated in the genesis of cell dysfunction in CRF. Therefore, it is reasonable to propose that the PTH-induced rise in [Ca2+]i provides a negative feedback control system for the down-regulation of the mRNA of the PTH-PTHrP in order to protect the cells from the harmful effects of progressive rise in blood levels of PTH in CRF. The heart contains the mRNA for this receptor and it is a target organ for PTH action. We examined whether the message of the PTH-PTHrP receptor is down-regulated in the heart of CRF animals and evaluated the role of [Ca2+]i in this process. The expression of the mRNA of the PTH-PTHrP was significantly reduced in the heart of CRF rats as compared to normal animals. Also, the CRF rats had elevated blood levels of PTH and high [Ca2+]i of cardiac myocytes. The parathyroidectomy of CRF rats prevented the rise in blood PTH levels and normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels. The treatment of CRF rats with verapamil normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels, despite marked elevation of blood levels of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

Elevated cytosolic calcium of adipocytes in chronic renal failure.

Chronic renal failure (CRF) is associated with increased calcium content of, and impaired lipase release from lipid cells. This has been attributed to a rise in the cytosolic calcium ([Ca2+]i) of these cells. However, data on [Ca2+]i of lipid cells in CRF and on the mechanisms responsible for such an abnormality are lacking. To study this issue we examined the [Ca2+]i and ATP content of lipid cells and Vmax of Na(+)-K(+)-ATPase and Ca2+ ATPase of membrane preparation and Na(+)-Ca2+ exchange of membrane vesicles of adipocytes from normal rats, 6 week CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) and CRF, and normal rats treated with verpamil (CRF-V, normal-V). [Ca2+]i in adipocytes of CRF rats was higher (199 +/- 8.5 nM) and ATP lower (2.9 +/- 0.31 nmol/10(6) cells) than in normal (120 +/- 4.3 nM; 5.7 +/- 0.27 nmol/10(6) cells), CRF-PTX (128 +/- 4.7 nM; 5.8 +/- 0.39 nmol/10(6) cells), normal-V (121 +/- 3.2 nM; 5.3 +/- 0.36 nmol/10(6) cells), CRF-V (123 +/- 7.4 nM; 5.5 +/- 0.30 mmol/10(6) cells). Vmax Ca2+ ATPase and the activity of Na(+)-K(+)-ATPase and of Na(+)-Ca2+ exchanger were reduced in CRF rats as compared to the other four groups of rats. The values in normal, CRF-PTX, CRF-V and normal-V rats were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Impaired agonist-induced calcium signaling in hepatocytes from chronic renal failure rats.

Some hormones exert their action by inducing a rise in cytosolic calcium [Ca2+]i (calcium signal), and therefore, a blunting in hormone-induced calcium signal would engender resistance to the action of the hormone. Chronic renal failure (CRF) is associated with resistance to the action of a variety of hormones, a rise in [Ca2+]i and decrease in the amount of mRNA of one hormone receptor, the PTH-PTHrP receptor. We examined the calcium-signal induced by PTH, angiotensin II, vasopressin and glucagon in hepatocytes from CRF animals, evaluated the effect of the basal level [Ca2+]i on the calcium signal and explored the effect of [Ca2+]i on the mRNA of the receptors of these agonists. Hepatocytes from CRF rats have elevated basal levels of [Ca2+]i and display significantly reduced calcium signals induced by all these hormones, while the calcium signals were normal in PTX-CRF animals and those treated with verapamil both of which have normal levels of [Ca2+]i despite CRF. The calcium signals induced by dibutyryl cyclic AMP and G protein activator (GTP gamma S) were normal in hepatocytes from CRF animals despite the high levels of [Ca2+]i. Northern blotting experiments revealed that the levels of the mRNA of the receptors of PTH-PTHrP, angiotensin II and vasopressin were significantly reduced in hepatocytes from CRF animals but PTX-CRF rats and those treated with verapamil had either significantly greater or even normal amounts of the mRNA of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Function and metabolism of brain synaptosomes in chronic renal failure.

Patients with advanced renal failure have derangements in the function of their nervous system. The available clinical and experimental data indicate that the state of the secondary hyperparathyroidism of renal failure plays a major role in the genesis of the nervous system dysfunction. The excess parathyroid hormone (PTH) mediates its deleterious effect by causing an elevation in cytosolic calcium of brain cells. This report reviews the evidence leading to the conclusion that PTH is a major uremic toxin.

Acetylcholine↗
PubMed1995

Chronic renal failure increases cytosolic Ca2+ of hepatocytes.

Chronic renal failure (CRF) is associated with increased Ca2+ content of liver and reduced hepatic lipase activity. This has been attributed to a rise in cytosolic Ca2+ ([Ca2+]i) of the hepatocytes, but data on this issue are lacking. We examined the [Ca2+]i and ATP content of hepatocytes as well as the activity of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), Ca(2+)-ATPase, and Na+/Ca2+ exchanger of hepatic membrane vesicles from normal rats, animals with 6 wk of CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) rats, and CRF and normal animals treated with verapamil (CRF-V, normal-V). [Ca2+]i in hepatocytes of CRF rats was higher (281 +/- 7.4 nM) and ATP lower (6.4 +/- 1.8 nmol/mg protein) than in normal (209 +/- 5.3 nM; 12.5 +/- 0.89 nmol/mg protein), CRF-PTX (212 +/- 1.0 nM; 13.7 +/- 0.79 nmol/mg protein), normal-V (215 +/- 2.3 nM; 14.2 +/- 0.77 nmol/mg protein), and CRF-V rats (209 +/- 7.4 nM; 14.8 +/- 0.72 nmol/10(6) cells). The Na(+)-K(+)-ATPase, the maximal velocity of Ca(2+)-ATPase, and the activity of the Na+/Ca2+ exchanger were reduced, whereas the Michaelis constant of Ca(2+)-ATPase was increase in CRF rats compared with the other four groups of rats. The values in the latter groups were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Pathways involved in PTH-induced rise in cytosolic Ca2+ concentration of rat renal proximal tubule.

Parathyroid hormone (PTH) raises cytosolic Ca2+ concentration ([Ca2+]i) in isolated or cultured renal proximal tubule cells. The pathways through which this action is mediated are not fully delineated. This study explored these pathways utilizing fura 2. [Ca2+]i of freshly prepared renal proximal tubular cells increased from 150 +/- 3.6 to 281 +/- 9.0 nM after the exposure to 10(-7) M angiotensin II, which served as a positive control. Both PTH-(1-84) and PTH-(1-34) produced a dose-dependent rise in [Ca2+]i. The effects of both moieties were similar up to 10(-7) M, but with higher doses the rise in [Ca2+]i with PTH-(1-84) was greater (P < 0.01) than with PTH-(1-34). This effect of the hormone occurred in the presence or absence of calcium in the media, but the rise in [Ca2+]i was significantly greater in the presence of calcium. The PTH-induced rise in [Ca2+]i was markedly inhibited by PTH antagonist [Nle8,18,Tyr34]bPTH-(7-34)-NH2 (bPTH is bovine PTH), verapamil, or nifedipine. 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, increased [Ca2+]i of cells, but its effect was less than PTH. Staurosporine abolished the TPA effect and partially inhibited that of PTH. A G protein activator raised [Ca2+]i, whereas a G protein inhibitor and pertussis toxin partially blocked the effect of PTH. Sodium or chloride channel blockers or sodium-free media did not modify the effect of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

PTH, chronic renal failure and myocardium.

The heart is a target organ for parathyroid hormone (PTH), and the action of this hormone on the myocardium may be mediated through the ability of PTH to increase cytosolic calcium ([Ca2+]i) in the myocardial cells. Such a property of PTH may be responsible for rise in [Ca2+]i in chronic renal failure (CRF). Our study examined these issues. The data from this study showed: (1) PTH increases [Ca2+]i of cardiac myocytes, (2) this action is receptor-mediated and is produced by activation of the L-type calcium channels following stimulation of G protein(s), (3) the rise in [Ca2+]i is due to both augmented entry of calcium into the myocytes and mobilization of calcium from sarcoplasmic reticulum by a calcium-induced calcium release mechanism, (4) CRF is associated with a significant rise in basal levels of [Ca2+]i of cardiac myocytes, (5) this effect is mediated by the state of secondary hyperparathyroidism of CRF, and (6) the pathways through which excess PTH in CRF generates this effect include both increased entry of calcium into cardiac myocytes and decreased exit of this ion out of these cells.

Animals↗