Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes

1997 ◽  
Vol 273 (5) ◽  
pp. E922-E931 ◽  
Author(s):  
M. C. Rebsamen ◽  
D. J. Church ◽  
D. Morabito ◽  
M. B. Vallotton ◽  
U. Lang
Keyword(s):  
Calcium Influx ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Endothelin 1 ◽  
Kinase C ◽  
Ventricular Cardiomyocytes ◽  
Camp Formation ◽  
Prostacyclin Production

The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETAreceptor (dissociation constant = 54 ± 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3′,5′-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETAreceptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.

scholarly journals Role of prostaglandin-mediated cyclic AMP formation in protein kinase C-dependent secretion of atrial natriuretic peptide in rat cardiomyocytes

1994 ◽  
Vol 303 (1) ◽  
pp. 217-225 ◽  
Author(s):  
D J Church ◽  
V Van der Bent ◽  
M B Vallotton ◽  
U Lang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Rat Cardiomyocytes ◽  
Endogenous Prostaglandin ◽  
Kinase C ◽  
Camp Formation

The role of endogenous prostaglandin production in phorbol diester-induced myocardial atrial natriuretic peptide (ANP) secretion was investigated in cultured spontaneously beating ventricular rat cardiomyocytes. Incubation of cells with 4 beta-phorbol 12-myristate 13-acetate (PMA; 0.1 microM) led to a rapid response in ANP release, a response accompanied by increases in cellular prostacyclin (PGI2) production, cyclic AMP (cAMP) formation and spontaneous contraction frequency. Although PMA-induced ANP secretion exhibited the pharmacological profile of a protein kinase C (PKC)-mediated event, the response was abolished in the presence of the cyclo-oxygenase inhibitors indomethacin (10 microM) and diclofenac (1 microM), indicating that endogenous prostaglandin production is responsible for PMA-induced ANP secretion in this system. Confirming this, PMA-induced ANP secretion was strongly correlated with endogenous formation of 6-oxo-prostaglandin F1 alpha (r = 0.93, P < 0.0005, n = 11), and exogenously applied PGI2, prostaglandin E2 (PGE2) or prostaglandin F2 alpha (PGF2 alpha) elicited simultaneous increases in cAMP formation, contraction frequency and ANP secretion in these cells. Furthermore, PMA-induced cAMP formation was abolished in the presence of either diclofenac or indomethacin, whereas the cAMP-elevating agent forskolin (0.1 microM) mimicked the secretory and chronotropic effect of PMA in these cells. A role for cAMP in PMA-induced ANP secretion was also apparent insofar as PMA-induced ANP release was substantially decreased in the presence of the Rp-diastereomer of 3′,5′-cyclic adenosine monophosphorothioate (Rp-cAMPS; 10 microM), whereas the cAMP-mimetic agent dibutyryl cAMP (10 microM) provoked a rapid increase in ANP secretion in this system. Finally, the Ca(2+)-channel antagonist nifedipine (0.1 microM) severely decreased PGI2-, PGE2- and PMA-induced ANP secretion without affecting PGF2 alpha-induced peptide release, suggesting that PGI2 and/or PGE2, but not PGF2 alpha, are the prostanoids involved in PMA-induced ANP release. Taken together, these results suggest that PKC activation induces ANP secretion in spontaneously beating rat ventricular cardiomyocytes via an autocrine pathway involving increased PGI2 and/or PGE2 formation, a response leading to the activation of a myocardial adenylate cyclase and, subsequently, to that of a nifedipine-sensitive Ca2+ channel.

scholarly journals Peroxisomes contribute to intracellular calcium dynamics

2020 ◽  
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
Sven Thoms
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

AbstractPeroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Further, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes can take up calcium in a controlled manner. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics by serving as buffers or sources of intracellular calcium.

scholarly journals Trophic effect of angiotensin II in neonatal rat cardiomyocytes: role of endothelin-1 and non-myocyte cells

1997 ◽  
Vol 121 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Klaus Pönicke ◽  
Ingrid Heinroth-Hoffmann ◽  
Karin Becker ◽  
Otto-Erich Brodde
Keyword(s):  
Angiotensin Ii ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Trophic Effect ◽  
Endothelin 1 ◽  
Neonatal Rat Cardiomyocytes

Antagonism of endothelin-1 inhibits hypoxia-induced apoptosis in cardiomyocytesThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (8) ◽  
pp. 536-540 ◽  
Author(s):  
Anjing Ren ◽  
Xiaohong Yan ◽  
Hong Lu ◽  
Jingsong Shi ◽  
Yuanjun Yin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Annexin V ◽  
Neonatal Rat ◽  
Receptor Subtypes ◽  
Rat Cardiomyocytes ◽  
Endothelin 1 ◽  
Apoptosis Rate ◽  
Hypoxic Conditions ◽  
Induced Apoptosis

Apoptosis is well documented to be a common feature of many pathological processes of the heart. Exogenous endothelin-1 (ET-1) has been shown to be proapoptotic or antiapoptotic, depending on ET-1 concentration, cell type, and the ratio of ETA/ETB receptor subtypes. The role of endogenous ET-1 in cardiomyocyte apoptosis, however, is not clarified. This study observed the effects of the ETA-receptor antagonists BQ610 and BQ123 and the ETB-receptor antagonist BQ788 on hypoxia-induced apoptosis in primary cultured neonatal rat cardiomyocytes. Hypoxic apoptosis was induced by incubating cardiomyocytes in serum-free medium under 3% O2 and 5% CO2 for 24 h and evaluated by TUNEL analysis and flow cytometry. TUNEL analysis showed that the apoptotic cardiomyocytes constituted 24.2% ± 2.2% of the total cells under hypoxic conditions. Treatment with BQ610 (5 μmol/L) significantly reduced the apoptosis rate to 13.2% ± 3.7% (data from 4 independent experiments, p < 0.01 vs. hypoxia). Flow cytometry showed that the percentage of apoptotic cells positively stained with annexin V and propidium iodide was 42.76% ± 4.44% (n = 12) in cultures subjected to hypoxia. BQ123 at 0.04, 0.2, and 1.0 μmol/L dose-dependently reduced the apoptosis rate to 34.00% ± 10.35% (n = 6, p < 0.05), 30.38% ± 8.28% (n = 6, p < 0.01), and 22.89% ± 4.19% (n = 6, p < 0.01), respectively. In contrast, BQ788 did not affect hypoxic apoptosis. These findings suggested that endogenous ET-1 contributed to hypoxia-induced apoptosis in cultured cardiomyocytes, which was mediated by ETA receptors, but not by ETB receptors.

scholarly journals Peroxisomes contribute to intracellular calcium dynamics in cardiomyocytes and non-excitable cells

2021 ◽  
Vol 4 (9) ◽  
pp. e202000987
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Christine S Gibhardt ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

Peroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Furthermore, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes can take up calcium. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected both in HeLa cells and in cardiomyocytes. Cardiac peroxisomes take up calcium on beat-to-beat basis. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics of cardiomyocytes.

Calcium influx in platelet activating factor-induced atrial natriuretic peptide release in rat cardiomyocytes

1994 ◽  
Vol 266 (3) ◽  
pp. E403-E409 ◽  
Author(s):  
D. J. Church ◽  
V. van der Bent ◽  
M. B. Vallotton ◽  
A. M. Capponi ◽  
U. Lang
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Calcium Channel ◽  
Natriuretic Peptide ◽  
Calcium Influx ◽  
Platelet Activating Factor ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Peptide Release ◽  
Camp Formation ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) is released from the myocardium after the activation of protein kinase C and/or ischemia, events that are associated with an increase in platelet activating factor (PAF) production in this tissue. In this study we demonstrate that PAF, but not lyso-PAF, induces a concentration-dependent increase in ANP secretion in spontaneously beating neonatal rat cardiomyocytes, a response associated with increases in cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation, calcium influx, and the mobilization of calcium from intracellular stores. cAMP formation and calcium influx appear to play major roles in PAF-induced ANP secretion in this system, insofar as PAF-induced ANP release was substantially reduced in the presence of the (R)-p-diastereoisomer of adenosine 3',5'-cyclic monophosphorothioate (10 microM), whereas both PAF-induced calcium influx and ANP secretion were abolished in the presence of the calcium channel antagonist nifedipine (0.1 microM). Consistent with these results, N6-2'-O-dibutyryl cAMP (DBcAMP, 10 microM) and/or forskolin (0.1 microM) simultaneously increased cAMP production, calcium influx, and ANP release in these cells, with both DBcAMP- and forskolin-induced ANP secretion being fully abolished in the presence of 0.1 microM nifedipine. Taken together, these results suggest that PAF, DBcAMP, and forskolin promote ANP secretion in spontaneously beating cardiomyocytes via the activation of a cAMP-dependent, nifedipine-sensitive myocardial calcium channel and that calcium influx is a major requirement for cAMP-induced ANP secretion in this system.

Cytochrome P-450 metabolites in endothelin-stimulated cardiac hormone secretion

2004 ◽  
Vol 286 (5) ◽  
pp. R888-R893 ◽  
Author(s):  
Sook Jeong Lee ◽  
Carol S. Landon ◽  
Stanley J. Nazian ◽  
John R. Dietz
Keyword(s):  
Protein Kinase ◽  
Inhibitory Action ◽  
Ventricular Myocytes ◽  
Hormone Secretion ◽  
Neonatal Rat ◽  
Kinase C ◽  
Neonatal Rat Ventricular Myocytes ◽  
Cytochrome P 450 ◽  
Kinase A

We examined the role of cytochrome P-450-arachidonate (CYP450-AA) metabolites in endothelin-1 (ET-1)-stimulated atrial natriuretic peptide (ANP) and pro-ANP-(1-30) secretion from the heart. 17-Octadecynoic acid (17-ODYA, 10-5 M) significantly inhibited ANP secretion stimulated by ET-1 (10-8 M) in the isolated perfused rat atria and inhibited pro-ANP-(1-30) secretion stimulated by ET-1 (10-8 M) or 20-hydroxyeicosatetraenoic acid in cultured neonatal rat ventricular myocytes (NRVM). In NRVM, 17-ODYA significantly ( P < 0.05) increased secretion of cAMP but had no significant effect on the secretion of cGMP from NRVM. Staurosporine, an inhibitor of protein kinase C, completely blocked the inhibitory action of 17-ODYA, whereas a protein kinase A inhibitor, H-89 (5 × 10-5 M), did not significantly attenuate the effects of 17-ODYA. The results show that the inhibitory action of 17-ODYA on ET-1-augmented ANP secretion is mediated through cAMP and suggest that CYP450-AA may play an important role in ET-1-induced cardiac hormone secretion.

scholarly journals MicroRNA-204 Is Necessary for Aldosterone-Stimulated T-Type Calcium Channel Expression in Cardiomyocytes

2018 ◽  
Vol 19 (10) ◽  
pp. 2941 ◽  
Author(s):  
Riko Koyama ◽  
Tiphaine Mannic ◽  
Jumpei Ito ◽  
Laurence Amar ◽  
Maria-Christina Zennaro ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Calcium Currents ◽  
Neonatal Rat ◽  
Messenger Rnas ◽  
Screening Assay ◽  
Rat Cardiomyocytes ◽  
Ventricular Cardiomyocytes ◽  
Channel Expression ◽  
Beating Frequency

Activation of the mineralocorticoid receptor (MR) in the heart is considered to be a cardiovascular risk factor. MR activation leads to heart hypertrophy and arrhythmia. In ventricular cardiomyocytes, aldosterone induces a profound remodeling of ion channel expression, in particular, an increase in the expression and activity of T-type voltage-gated calcium channels (T-channels). The molecular mechanisms immediately downstream from MR activation, which lead to the increased expression of T-channels and, consecutively, to an acceleration of spontaneous cell contractions in vitro, remain poorly investigated. Here, we investigated the putative role of a specific microRNA in linking MR activation to the regulation of T-channel expression and cardiomyocyte beating frequency. A screening assay identified microRNA 204 (miR-204) as one of the major upregulated microRNAs after aldosterone stimulation of isolated neonatal rat cardiomyocytes. Aldosterone significantly increased the level of miR-204, an effect blocked by the MR antagonist spironolactone. When miR-204 was overexpressed in isolated cardiomyocytes, their spontaneous beating frequency was significantly increased after 24 h, like upon aldosterone stimulation, and messenger RNAs coding T-channels (CaV3.1 and CaV3.2) were increased. Concomitantly, T-type calcium currents were significantly increased upon miR-204 overexpression. Specifically repressing the expression of miR-204 abolished the aldosterone-induced increase of CaV3.1 and CaV3.2 mRNAs, as well as T-type calcium currents. Finally, aldosterone and miR-204 overexpression were found to reduce REST-NRSF, a known transcriptional repressor of CaV3.2 T-type calcium channels. Our study thus strongly suggests that miR-204 expression stimulated by aldosterone promotes the expression of T-channels in isolated rat ventricular cardiomyocytes, and therefore, increases the frequency of the cell spontaneous contractions, presumably through the inhibition of REST-NRSF protein.

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