New actions of parathyroid hormone. Introduction.
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Humans↗
Biomedical subjects
M Smogorzewski
Publications and source records attributed to M Smogorzewski.
Hypokalemic effects of intravenous infusion or nebulization of salbutamol in patients with chronic renal failure: comparative study.
To examine and compare the efficacy and safety of different routes of administration of salbutamol in treating hyperkalemia, 15 patients with chronic renal failure (blood urea nitrogen > 80 mg/dL, serum creatinine > 8.0 mg/dL) were enrolled to sequentially receive either intravenous infusion (0.5 mg) or nebulization (10 mg) of salbutamol. Five of these patients (33.3%) did not respond to the intravenous salbutamol and were excluded from the study. Both treatments significantly decreased plasma potassium in 10 patients and the decrease was sustained for at least 3 hours. After infusion, the maximal reduction in plasma potassium levels was 0.92 +/- 0.10 mEq/L and occurred after 30 minutes. On the other hand, the maximal reduction in plasma potassium after nebulization (0.85 +/- 0.13 mEq/L) was similar to that after infusion, but it occurred after 90 minutes. Insulin and blood glucose increased, whereas blood pH, PCO2, sodium, osmolality, and blood pressure did not change after either treatment. Heart rate increased significantly after both treatments, but less after nebulization than after infusion. It is concluded that both infusion and nebulization are simple, effective, and safe therapeutic modalities for the treatment of hyperkalemia in patients with chronic renal failure. Infusion should be used in patients requiring a rapid decrease in plasma potassium; nebulization, on the other hand, should be used in patients with coronary artery diseases.
Administration, Inhalation↗
Altered cytosolic calcium homeostasis in rat cardiac myocytes in CRF.
Chronic renal failure (CRF) is associated with an increase in calcium content of heart. This was attributed to the secondary hyperparathyroidism of CRF, since PTH augments entry of calcium into cardiac myocytes. At present, it is not known whether the increase in calcium content of heart reflects a rise in basal levels of cytosolic calcium ([Ca2+]) of cardiac myocytes. Further, in order for the PTH-induced entry of calcium into cardiac myocytes to raise their basal levels of [Ca2+]i, calcium extrusion out of these cells should be impaired as well. The present study examined the effect of CRF with and without excess PTH (PTX) and of the treatment of CRF rats with verapamil on basal levels of [Ca2+]i and ATP content of cardiac myocytes and on the activities of the pumps that are directly (Ca(2+)-ATPase and Na(+)-Ca2+ exchanger) and indirectly (Na(+)-K+ ATPase) responsible for calcium extrusion out of these cells. The basal levels of [Ca2+]i of cardiac myocytes increased (P < 0.01) and their ATP content decreased (P < 0.01) as the duration of CRF advanced. CRF was associated with significant decrement in Vmax of Ca2+ ATPase and Na(+)-K+ ATPase and in Na(+)-Ca2+ exchange. These derangements were prevented by prior PTX of the CRF rats or by their treatment with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Mechanisms of PTH-induced rise in cytosolic calcium in adult rat hepatocytes.
Available data indicate that the liver is a target organ for parathyroid hormone (PTH) and that this effect is most likely mediated by PTH-induced calcium entry into hepatocytes. The present study examined the effects of both PTH-(1-84) and its amino-terminal fragment [PTH-(1-34)] on cytosolic calcium concentration ([Ca2+]i) of hepatocytes and explored the cellular pathways that mediate this potential action of PTH. Both moieties of PTH produced a dose-dependent rise in [Ca2+]i, but the effect of PTH-(1-84) was greater (P < 0.01) than an equimolar amount of PTH-(1-34). This effect required calcium in the medium and was totally [PTH-(1-34)] or partially [PTH-(1-84)] blocked by PTH antagonist ([Nle8,18,Tyr34]bPTH-(7-34)-NH2] and by verapamil or nifedipine. Sodium or chloride channel blockers did not modify this effect. 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), and G protein activator also produced a dose-dependent rise in [Ca2+]i. Staurosporine abolished the effect of TPA, and both staurosporine and calphostin C partially inhibited the effect of PTH. Staurosporine and verapamil together produced greater inhibition of PTH action than each alone. Rp-cAMP, a competitive inhibitor of cAMP binding to the R subunit of protein kinase A, and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a protein kinase A inhibitor, blocked the effect of both DBcAMP and PTH, but the effect of these agents was greater (P < 0.01) on DBcAMP action. G protein inhibitor and pertussis toxin partially blocked the action of PTH. The data indicate that 1) PTH increases [Ca2+]i of hepatocytes; 2) this action of the hormone is receptor mediated; 3) the predominant pathway for this PTH action is the stimulation of a G protein-adenylate cyclase-cAMP system, which then leads to stimulation of a calcium transport system inhibitable by verapamil or nifedipine or activation of L-type calcium channels; 4) activation of protein kinase C is also involved; and 5) the PTH-induced rise in [Ca2+]i is due, in major parts, to movement of extracellular calcium into the cell.
Animals↗
Abnormal leucine-induced insulin secretion in chronic renal failure.
Chronic renal failure (CRF) is associated with a sundry of abnormalities in pancreatic islets including a rise in their cytosolic calcium, reduced ATP content, and impaired glucose-induced insulin secretion. The latter is also stimulated by amino acids (such as leucine), and the cellular processes involved in leucine-induced insulin secretion are different from those responsible for glucose-induced insulin release. The present study examined whether leucine-induced insulin secretion is also impaired in CRF and investigated the cellular derangements for such a potential abnormality. The results showed that leucine-induced insulin secretion is markedly reduced by islets from CRF animals, and this defect was prevented by parathyroidectomy (PTX) of the CRF animals or by their treatment with verapamil, an agent that blocks the action of parathyroid hormone (PTH) on the pancreatic islets. Both leucine uptake and alpha-ketoisocaproic acid-induced insulin secretion by islets from CRF rats are normal; however, both the activation of glutamate dehydrogenase (GLDH) by leucine or by 2-aminobicyclo-[2-2-1]-haptene and the utilization of alpha-ketoglutarate are impaired, and the maximal reaction rate (Vmax) of glutaminase is reduced. These derangements are corrected by PTX of CRF rats or by their treatment with verapamil. The data demonstrate that 1) CRF is associated with impaired leucine-induced insulin secretion, 2) this defect is due to the state of secondary hyperparathyroidism of CRF, and 3) the cellular derangements responsible for this defect involve abnormalities in the metabolism of leucine and derangements in the leucine-GLDH-alpha-ketoglutarate-glutaminase pathway of the islets.
Animals↗
PTH-PTHrP receptor mRNA is downregulated in chronic renal failure.
Resistance to the action of PTH is encountered in chronic renal failure (CRF). This was attributed to downregulation of PTH receptor due to the state of secondary hyperparathyroidism of CRF. The present study examined whether the amount of PTH-PTH-related peptide (PTH-PTHrP) mRNA in a traditional (kidney) and a nontraditional (liver) organs for PTH action was reduced in CRF. PTH-PTHrP mRNA was measured in kidney and liver obtained from normal rats, animals with CRF of 6 weeks' duration, normocalcemic parathyroidectomized CFR rats and from CRF and normal rats treated with verapamil. The mRNA of receptor was quantitated with Northern blot analysis of kidney RNA and liver poly A+ RNA. The relative amounts of mRNA of the PTH-PTHrP receptor to that of beta-actin in both kidney and liver of CRF rats were significantly (p < 0.01) lower than in normal animals. Parathyroidectomy of CRF rats was followed either by significant (p < 0.01) improvement (kidney) or normalization (liver) of the receptor mRNA. Treatment of CRF rats with verapamil also significantly (p < 0.01) improved the concentration of the receptor mRNA in the kidney. The data demonstrate that CRF is associated with downregulation of the PTH-PTHrP receptor mRNA in kidney and liver. This defect is partially or completely reversed by parathyroidectomy of the CRF rats or their treatment with verapamil. The decrease in the receptor mRNA would likely result in a decrease in PTH receptor synthesis and consequently PTH receptor numbers, and hence relative resistance to the action of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Sequence of appearance of the metabolic derangements in rat brain synaptosomes during phosphate depletion.
Chronic phosphate depletion (PD) causes a rise in basal level of cytosolic calcium ([Ca2+]i) in rat brain synaptosomes, a decrease in their ATP content and a reduction in Vmax of their Ca2+ ATPase and Na(+)-K+ ATPase. The chronology of the events that lead to these derangements is not elucidated. The present study examined this issue by evaluating the changes in rat in these parameters in brain synaptosomes during the evolution of PD over a period of 6 weeks. The results show that the initial derangement is a rise in the Vmax of Ca2+ ATPase during the first 2 weeks of PD. This is followed by a rise in [Ca2+]i, a fall in ATP content and decrease in the Vmax of Ca2+ ATPase and Na(+)-K+ ATPase by the end of the 3 week and most of these derangement worsened during the 4th to 6th weeks of PD. Taken together our data are consistent with the notion that PD is associated with an initial increase in calcium influx into the synaptosomes. This is followed by a modest but significant rise in [Ca2+]i which in turn would inhibit mitochondrial oxidation and ATP generation leading to a decrease in ATP content. The latter compromises the activity of Ca2+ ATPase and Na(+)-K+ ATPase which are involved, directly or indirectly, in calcium extrusion out of the synaptosomes. The increased entry of calcium combined with decreased calcium extrusion are followed by a further rise in basal levels of [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Effects of parathyroid hormone on cytosolic calcium of rat adipocytes.
Available data indicate that adipocytes are targets for PTH action, and chronic excess of PTH increases calcium burden of fat tissue, suggesting that PTH increases entry of calcium into adipocytes. The present study examined the effects of PTH-(1-84) and its amino-terminal fragment, PTH-(1-34), on cytosolic calcium ([Ca2+]i) of adipocytes and evaluated the cellular pathways that mediate the potential effect of PTH on [Ca2+]i of these cells. PTH-(1-84) but not PTH-(1-34) produced a dose-dependent rise in [Ca2+]i of adipocytes. This effect occurred in the presence or absence of calcium in the media, but the magnitude of the rise in [Ca2+]i was significantly greater when calcium was present in the media. The PTH antagonist [Nle8,18Tyr34]bPTH(7-34)NH2, verapamil, and nifedipine blocked to variable degrees the PTH-induced rise in [Ca2+]i. The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate, and the GTP-binding protein (G protein) GTP gamma S also produced a dose-dependent rise in [Ca2+]i of adipocytes. These effects were inhibited by staurosporine and the G protein inhibitor guanosine 5'-O-1(2-thiodiphosphate), respectively. Similary, staurosporine, calphostin C, guanosine 5'-O-1(2-thiodiphosphate), and pertussis toxin inhibited the effect of PTH on [Ca2+]i of adipocytes. (Bu)2cAMP also increased [Ca2+]i of adipocytes, but PTH did not stimulate cAMP production by adipocytes, and N-[2(p-bromocin-namylamino)ethyl]5-isoquinoline-sulfonamide, an inhibitor of protein kinase A, did not affect the PTH-induced rise in [Ca2+]i of adipocytes. The data indicate that: 1) PTH-(1-84) increases [Ca2+]i of adipocytes; 2) this action of the hormone is receptor mediated; 3) the hormone uses a G protein activation of calcium channels and the phospholipase C pathway in mediating its action on [Ca2+]i; and 4) the rise in [Ca2+]i is due to both increased calcium influx into the adipocytes and mobilization of calcium from intracellular stores.
Adipocytes↗
Phosphate depletion impairs leucine-induced insulin secretion.
Phosphate depletion (PD) in vivo causes a sundry of abnormalities in pancreatic islets including a rise in cytosolic calcium, low ATP content, reduced Ca2+ ATPase and Na(+)-K+ ATPase activity, and impaired insulin secretion in response to glucose or potassium. L-Leucine is a strong secretagogue that triggers insulin secretion by deamination to alpha-ketoisocaproic acid (KIC) and the subsequent metabolism of the latter to ATP and by the activation of glutamate dehydrogenase (GLDH), which acts on glutamate to generate alpha-ketoglutarate, the metabolism of which results in ATP production. The generation of ATP triggers events that lead to insulin secretion. It is not known whether PD impairs leucine-induced insulin secretion, and the cellular derangements that are involved in such an abnormality are not defined. These issues were studied in PD rats and in pair-weighed normal animals as controls. D-Leucine uptake by islets from PD rats is normal, but both leucine- and KIC-induced insulin secretions are impaired and the activity of branched-chain keto acid dehydrogenase, which facilitates the metabolism of KIC, is reduced. Both leucine and 2-aminobicyclo (2-2-1) haptene failed to stimulate GLDH and to augment the generation of alpha-ketoglutarate in the islets of PD rats. Also, the concentration of basal alpha-ketoglutarate was significantly higher in the islets of PD rats, suggesting that its metabolism is impaired. In addition, the activity of glutaminase is significantly reduced, an abnormality that would result in decreased production of glutamate, the substrate for GLDH. The data show that PD impairs leucine-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Mechanisms through which parathyroid hormone mediates its deleterious effects on organ function in uremia.
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Humans↗
Verapamil prevents chronic renal failure-induced abnormalities in lipid metabolism.
Hypertriglyceridemia is common in chronic renal failure (CRF); this derangement is due to decreased peripheral removal of triglycerides. Certain data indicate that the state of secondary hyperparathyroidism of CRF is, at least in part, responsible for derangements in lipid metabolism. It has been proposed that chronic excess of parathyroid hormone exerts its deleterious effects on many organs through its ability to raise basal levels of cytosolic calcium. Prevention of the latter by a calcium channel blocker is followed by the correction of organ dysfunctions. The present study examined the effect of treatment of CRF rats with verapamil on several parameters of lipid metabolism. Chronic renal failure rats displayed hypertriglyceridemia, fat intolerance, reduced postheparin plasma lipoprotein and hepatic lipase activities, decreased hepatic lipase in liver homogenate, and elevated calcium content in liver and epididymal fat. Treatment of the CRF rats with verapamil prevented all these derangements in lipid metabolism. These effects of verapamil were similar to those produced by parathyroidectomy of CRF rats. The data are consistent with the formulation that chronic excess of parathyroid hormone increases the calcium burden of liver and adipose tissue and consequently impairs the synthesis and/or release of lipoprotein and hepatic lipases. Reduced availability of these enzymes in plasma results in impared peripheral removal of triglycerides, leading to hypertriglyceridemia.
Animals↗
Derangements in acetylcholine metabolism in brain synaptosomes in chronic renal failure.
Chronic renal failure causes abnormalities in the central nervous system function and in norepinephrine metabolism of brain synaptosomes. The present study examined the effect of renal failure on the metabolism of another neurotransmitter, acetylcholine, which is involved in the modulation of behavioral and motor function. We measured acetylcholine content and release, choline content, uptake and release and activity of choline kinase in synaptosomes from rats with renal failure with various duration, renal failure-parathyroid-ectomized rats maintained normocalcemic, renal failure and normal rats treated with verapamil. Acetylcholine content increased while choline content decreased proportionally and significantly (P < 0.01) with the duration of renal failure; choline kinase activity was reduced (P < 0.01). These derangements were prevented by parathyroidectomy of renal failure rats or by their treatment with verapamil. Choline uptake and release were elevated in renal failure and these abnormalities were not corrected by parathyroidectomy or verapamil therapy. Acetylcholine release was elevated in renal failure and parathyroidectomy prevented this derangement. Verapamil reduced acetylcholine release in both normal and renal failure rats. The data show that: (a) renal failure causes significant derangements in acetylcholine metabolism leading to its accumulation in and an increase in its release from brain synaptosomes; (b) this is mainly due to reduced activity of choline kinase, most likely, mediated by the state of secondary hyperparathyroidism of renal failure; (c) blocking the parathyroid hormone-induced calcium influx into synaptosomes by verapamil prevented the abnormalities in acetylcholine metabolism; and (d) the derangement in choline uptake and release in CRF is not related to excess parathyroid hormone since parathyroidectomy or verapamil treatment did not correct them.
Acetylcholine↗
Parathyroid hormone raises cytosolic calcium in pancreatic islets: study on mechanisms.
The pancreatic islets of Langerhans are targets for PTH and the action of the hormone on the islet is most likely mediated through the ability of PTH to increase cytosolic calcium ([Ca2+]i) of the islet cells. Although direct evidence for such an effect has been clearly demonstrated, the mechanisms through which the hormone exerts such an action are not elucidated. The present study examined these questions using pancreatic islets isolated from normal rats. Both 1-34 and 1-84 PTH produced a dose dependent increase in [Ca2+]i of the islets but the effect of the latter was significantly (P < 0.01) greater than that of the former. This action of PTH was significantly (P < 0.01) decreased by the use of PTH antagonist or by verapamil. The G protein activator (GTP gamma S) mimicked the effect of PTH while pertussis toxin and the G protein inhibitor (GDP beta S) significantly reduced the PTH-induced rise in [Ca2+]i. Dibutyryl cAMP, and phorbol ester 12-myristate 13 acetate increased [Ca2+]i of pancreatic islets in a dose dependent manner and the effect was inhibited (P < 0.01) by verapamil. Staurosporine inhibited the effect of TPA as well as of 1-84 PTH on [Ca2+]i of the islets. These data indicate that: (1) PTH increases [Ca2+]i of pancreatic islets, (2) this action is partly receptor mediated and is produced by activation of L-type calcium channels through stimulation of G protein(s), and (3) the rise in [Ca2+]i is due to both stimulation of cAMP generation and activation of protein kinase C.
Alkaloids↗
Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes.
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. However, direct evidence for such an effect of PTH is lacking, and the mechanism(s) through which the hormone can potentially exert such an effect have not been elucidated. In the present study these questions were examined using cardiac myocytes isolated from adult rats. Both PTH-(1-34) and PTH-(1-84) produced a dose-dependent increase in [Ca2+]i of myocytes, but the effect of the latter was significantly (P < 0.01) greater than the former. This action of PTH was abolished by the inactivation of the hormone, the use of a PTH antagonist, or by verapamil. The G protein activator, guanosine 5'-O-(3-thiothriphosphate) (GTP gamma S), mimicked the effect of PTH, whereas pertussis toxin, the G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), or ryanodine significantly reduced the PTH-induced rise in [Ca2+]i. Dibutyryl- and 8-bromoadenosine-3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoylphorbol 13-acetate, and staurosporine did not increase [Ca2+]i in myocytes, and staurosporine did not alter the PTH-induced rise in [Ca2+]i. BAY K 8644 augmented the effect of PTH on [Ca2+]i. These data demonstrate that 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), and 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.
Animals↗
Abnormal norepinephrine metabolism in rat brain synaptosomes in phosphate depletion.
Abnormalities in the function of the central nervous system exist in phosphate depletion (PD). It is possible that this is due to an adverse effect of PD on the metabolism of neurotransmitters, such as norepinephrine (NE), in brain synaptosomes. We examined the effects of PD, produced by restriction of dietary phosphate intake on NE metabolism of brain synaptosomes. Synaptosomes from PD rats had significantly reduced NE content, uptake and release, elevated Km, but normal Vmax of tyrosine hydroxylase, normal Km and Vmax of monoamine oxidase, elevated resting levels of cytosolic calcium ([Ca2+]i), higher delta [Ca2+]i in response to KCl, higher delta [Ca2+]i/basal [Ca2+]i ratio, lower ATP content and reduced activity of Na(+)-K(+)-ATPase as compared to synaptosomes from pair-weighed rats. Treatment of PD rats with verapamil corrected all the synaptosomal derangements except for the elevated Km of tyrosine hydroxylase and NE content. Verapamil did not affect the metabolism of PW rats. The data demonstrate that PD causes significant derangements in NE metabolism of brain synaptosomes. Observations in the present study and in others indicate that these derangements in NE metabolism are due to the PD-induced abnormalities in the homeostasis of synaptosomal [Ca2+]i, ATP and phospholipids and in the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase.
Animals↗
Elevated basal levels of cytosolic calcium of thymocytes in chronic renal failure.
The basal levels of cytosolic calcium ([Ca2+]i) in rats and/or humans with chronic renal failure (CRF) are elevated in many cells including brain synaptosomes, pancreatic islets, polymorphonuclear leukocytes, platelets and B and T cells. This rise in [Ca2+]i has been attributed to the state of secondary hyperparathyroidism of CRF. These observations have led to the proposition that CRF is a state of cellular calcium intoxication mediated by excess parathyroid hormone (PTH). The documentation of a high basal level of [Ca2+]i in other cells is needed to provide further support for this postulate. The present study evaluated the basal levels of [Ca2+]i of thymocyte, which are targets for PTH action, in normal, CRF, and CRF parathyroidectomized (CRF-PTX) rats. We also examined whether CRF affects the phenotype expression (Thy-1, CD4 and CD8) in thymocytes. The results showed that the basal levels of [Ca2+]i in thymocytes from CRF rats (81 +/- 3.7 nM) are significantly (p < 0.01) higher than those in normal animals (60 +/- 2.9 nM). PTX of CRF animals prevented the elevation in the basal levels of [Ca2+]i of thymocytes; in these animals, the levels were 59 +/- 2.8 nM. Neither CRF nor the elevation in [Ca2+]i of thymocytes affected their phenotype expression.
Animals↗
Parathyroid hormone-parathyroid hormone related protein receptor messenger RNA is present in many tissues besides the kidney.
Parathyroid hormone (PTH) acts on a large number of cells derived from many different tissues that are not traditional targets (kidney and bone) for their action. Also, the acute exposure of many of these cells to PTH resulted in the generation of cAMP. These observations are consistent with the presence of PTH receptors on these cells. However, there is no evidence that the cells that are not traditional targets for PTH, express the receptor of the hormone. The cloning of the PTH-PTH related protein (PTH-PTHrP) receptor provided the tool to examine whether these cells contain the mRNA for this receptor. Poly A+RNA from a variety of rat tissues was probed with a 1,200-bp fragment of the cDNA of the PTH-PTHrP receptor by the Northern blot technique. We found that mRNA for the PTH-PTHrP receptor is present in the heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Transcripts of 2.4 kb were found in all these tissues with the strongest expression in the kidney. In addition, smaller RNAs were detected in the kidney (approximately 1.8 kb) and testis (1.5 kb). These results indicate that many cell types express the PTH-PTHrP receptor gene. The data provide a possible explanation for the direct effects of PTH on so many cells and for the understanding of the harmful effects of chronic excess of PTH on the function of many organs in chronic renal failure.
Animals↗
Parathyroid hormone increases cytosolic calcium of thymocytes.
Parathyroid hormone (PTH) has been implicated in the genesis of the abnormalities of the immune system in uremia. This action was attributed to the ability of PTH to augment entry of calcium and hence sustain an elevation of the basal level of cytosolic calcium ([Ca2+]i) in the cells of the immune system. However, direct evidence for such an action of the hormone on these cells is lacking. We examined whether PTH affects [Ca2+]i of rat thymocytes and the potential mechanisms of such an effect. 1-84 PTH (0.5, 1.0, 2.0 x 10(-7) M) increased [Ca2+]i in a dose-dependent manner by 31 +/- 2.6, 73 +/- 3.8, and 128 +/- 10.8 nM, respectively. 1-34 PTH had no effect. The various doses of PTH antagonist ([Tyr-34] bPTH (7-34)NH2) blocked the PTH-induced rise in [Ca2+]i by 41-67%. Dibutyryl adenosine 3',5'-cyclic phosphatase (cAMP), forskolin and phorbol ester 12-0-tetradecanoyl-phorbol 13-acetate (TPA) also produced a significant rise in [Ca2+]i of thymocytes. Verapamil blocked the PTH action by 44% but had no effect on the dibutyryl-cAMP-, forskolin- or TPA-induced rise in [Ca2+]i. Absence of calcium in the media abolished the PTH-induced increase in [Ca2+]i and significantly reduced that of dibutyryl cAMP. Staurosporine completely prevented the TPA-induced rise in [Ca2+]i but had no effect on that produced by PTH. 1-84 PTH in the presence of calcium in the medium produced a significant rise in thymocyte cAMP but had no effect in the absence of calcium in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗