Home LiteratureArticle Details
PMID: 9169501 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes.

The Journal of clinical investigation ·Vol. 99 ·No. 11 ·1997-06-01 ·Pages 2710-8

Rivet-Bastide M, Vandecasteele G, Hatem S, Verde I, Bénardeau A, Mercadier JJ, Fischmeister R

Abstract

EHNA (Erythro-9-[2-hydroxy-3-nonyl]adenine) is a wellknown inhibitor of adenosine deaminase. Recently, EHNA was shown to block the activity of purified soluble cGMPstimulated phosphodiesterase (PDE2) from frog, human, and porcine heart with an apparent Ki value of approximately 1 microM and with negligible effects on Ca2+/calmodulin PDE (PDE1), cGMP-inhibited PDE (PDE3), and low Km cAMP-specific PDE (PDE4) (Méry, P.F., C. Pavoine, F. Pecker, and R. Fischmeister. 1995. Mol. Pharmacol. 48:121-130; Podzuweit, T., P. Nennstiel, and A. Muller. 1995. Cell. Signalling. 7:733- 738). To investigate the role of PDE2 in the regulation of cardiac L-type Ca2+ current (ICa), we have examined the effect of EHNA on ICa in freshly isolated human atrial myocytes. Extracellular application of 0.1-10 microM EHNA induced an increase in the amplitude of basal ICa ( approximately 80% at 1 microM) without modification of the current-voltage or inactivation curves. The maximal stimulatory effect of EHNA on ICa was comparable in amplitude with the maximal effect of isoprenaline (1 microM), and the two effects were not additive. The effect of EHNA was not a result of adenosine deaminase inhibition, since 2'-deoxycoformycin (1-30 microM), another adenosine deaminase inhibitor with no effect on PDE2, or adenosine (1-10 microM) did not increase ICa. In the absence of intracellular GTP, the substrate of guanylyl cyclase, EHNA did not increase ICa. However, under similar conditions, intracellular perfusion with 0.5 microM cGMP produced an 80% increase in ICa. As opposed to human cardiomyocytes, EHNA (1-10 microM) did not modify ICa in isolated rat ventricular and atrial myocytes. We conclude that basal ICa is controlled by PDE2 activity in human atrial myocytes. Both PDE2 and PDE3 may contribute to keep the cyclic nucleotides concentrations at minimum in the absence of adenylyl and/or guanylyl cyclase stimulation.

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/metabolism Adenine/analogs & derivatives,pharmacology Animals Calcium/metabolism Cells, Cultured Cyclic Nucleotide Phosphodiesterases, Type 1 Enzyme Inhibitors/pharmacology Heart Atria/metabolism Humans Ion Transport/drug effects Rats
Chemicals
Enzyme Inhibitors 9-(2-hydroxy-3-nonyl)adenine 3',5'-Cyclic-AMP Phosphodiesterases Cyclic Nucleotide Phosphodiesterases, Type 1 Adenine Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rivet-Bastide M
Laboratoire de Cardiologie Cellulaire et Moléculaire, Institut National de la Santé et de la Recherche Médicale U-446, Université de Paris-Sud, Faculté de Pharmacie, F-92296 Châtenay-Malabry, France.
Vandecasteele G
Hatem S
Verde I
Bénardeau A
Mercadier J J
Fischmeister R
References (46)
46 references, click to expand
  1. Stimulation of adenosine 3',5'-monophosphate hydrolysis by guanosine 3',5'-monophosphate.
    J Biol Chem. 1971 Jun 25;246(12):3841-6 PMID: 4327188
  2. Acetylcholine inhibits Ca2+ current by acting exclusively at a site proximal to adenylyl cyclase in frog cardiac myocytes.
    J Physiol. 1996 Mar 15;491 ( Pt 3):669-75 PMID: 8815202
  3. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
    Pflugers Arch. 1981 Aug;391(2):85-100 PMID: 6270629
  4. erythro-9-[3-(2-Hydroxynonyl)]adenine is an effective inhibitor of cell motility and actin assembly.
    Proc Natl Acad Sci U S A. 1984 Oct;81(19):6044-8 PMID: 6385006
  5. Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells.
    Nature. 1986 Sep 18-24;323(6085):273-5 PMID: 2429189
  6. Erythro-9-[3-(2-hydroxynonyl)]adenine and vanadate as probes for microtubule-based cytoskeletal mechanochemistry.
    Methods Enzymol. 1986;134:477-87 PMID: 2950298
  7. G proteins: transducers of receptor-generated signals.
    Annu Rev Biochem. 1987;56:615-49 PMID: 3113327
  8. Cyclic guanosine 3',5'-monophosphate regulates the calcium current in single cells from frog ventricle.
    J Physiol. 1987 Jun;387:453-72 PMID: 2443683
  9. Cyclic GMP in cell function.
    Adv Second Messenger Phosphoprotein Res. 1988;22:319-83 PMID: 2906250
  10. Cyclic GMP regulates the Ca-channel current in guinea pig ventricular myocytes.
    Pflugers Arch. 1989 Apr;413(6):685-7 PMID: 2542886
  11. Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systems.
    Prog Biophys Mol Biol. 1988;52(3):165-247 PMID: 2477870
  12. Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram.
    Cell Signal. 1996 Feb;8(2):97-110 PMID: 8730511
  13. Regulation of myocardial calcium channels by cyclic AMP metabolism.
    Basic Res Cardiol. 1996;91 Suppl 2:1-8 PMID: 8957537
  14. Biphasic effects of intrapipette cyclic guanosine monophosphate on L-type calcium current and contraction of guinea pig ventricular myocytes.
    J Pharmacol Exp Ther. 1996 Dec;279(3):1274-81 PMID: 8968351
  15. Cyclic AMP phosphodiesterases and Ca2+ current regulation in cardiac cells.
    Life Sci. 1991;48(25):2365-76 PMID: 1646365
  16. Cardiac atrial natriuretic factor during evolution of congestive heart failure.
    Am J Physiol. 1992 Apr;262(4 Pt 2):H1248-55 PMID: 1373574
  17. Potentiation by cyclic GMP of beta-adrenergic effect on Ca2+ current in guinea-pig ventricular cells.
    J Physiol. 1991 Nov;443:387-404 PMID: 1668341
  18. Effects of atrionatriuretic factor on Ca2+ current and Cai-independent transient outward K+ current in human atrial cells.
    Pflugers Arch. 1992 Aug;421(5):486-91 PMID: 1281312
  19. Nitric oxide synthase activities in human myocardium.
    Lancet. 1993 Jan 9;341(8837):84-5 PMID: 7678120
  20. Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation.
    J Biol Chem. 1993 Dec 15;268(35):26286-95 PMID: 7902837
  21. Adenosine deaminase inhibitor in cardioplegia enhanced function preservation of the hypothermically stored rat heart.
    Transplantation. 1994 Jan;57(1):35-40 PMID: 8291112
  22. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells.
    Physiol Rev. 1994 Apr;74(2):365-507 PMID: 8171118
  23. Behaviour of human atrial myocytes in culture is donor age dependent.
    Neuromuscul Disord. 1993 Sep-Nov;3(5-6):385-90 PMID: 8186680
  24. An obligatory role for nitric oxide in autonomic control of mammalian heart rate.
    J Physiol. 1994 Apr 15;476(2):309-14 PMID: 7913969
  25. Increased nitric oxide production in heart failure.
    Lancet. 1994 Aug 6;344(8919):373-4 PMID: 7914309
  26. Existence and role of substrate cycling between AMP and adenosine in isolated rabbit cardiomyocytes under control conditions and in ATP depletion.
    Circulation. 1994 Sep;90(3):1343-9 PMID: 8087944
  27. Nitric oxide regulates the calcium current in isolated human atrial myocytes.
    J Clin Invest. 1995 Feb;95(2):794-802 PMID: 7860763
  28. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes.
    J Biol Chem. 1995 Jun 16;270(24):14582-6 PMID: 7540173
  29. Adenosine inhibits the L-type calcium current in human atrial myocytes.
    Naunyn Schmiedebergs Arch Pharmacol. 1995 Mar;351(3):293-7 PMID: 7609783
  30. Erythro-9-(2-hydroxy-3-nonyl)adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes.
    Mol Pharmacol. 1995 Jul;48(1):121-30 PMID: 7623766
  31. Recent progress in understanding the hormonal regulation of phosphodiesterases.
    Endocr Rev. 1995 Jun;16(3):370-89 PMID: 7671852
  32. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.
    Physiol Rev. 1995 Oct;75(4):725-48 PMID: 7480160
  33. A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate.
    J Gen Physiol. 1995 Jul;106(1):45-65 PMID: 7494138
  34. Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine.
    Cell Signal. 1995 Sep;7(7):733-8 PMID: 8519602
  35. Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart. Implications for adenosine metabolism.
    Circ Res. 1990 Mar;66(3):754-62 PMID: 1689616
  36. Neurohormonal control of calcium sensitivity of myofilaments in rat single heart cells.
    Circ Res. 1990 Aug;67(2):517-24 PMID: 2115824
  37. Regulation of calcium current by low-Km cyclic AMP phosphodiesterases in cardiac cells.
    Mol Pharmacol. 1990 Sep;38(3):426-33 PMID: 1698253
  38. Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1197-201 PMID: 1705030
  39. Immunoaffinity purification of soluble guanylyl cyclase.
    Methods Enzymol. 1991;195:391-6 PMID: 1674571
  40. Role of nitric oxide and phosphodiesterase isoenzyme II for reduction of endothelial hyperpermeability.
    Am J Physiol. 1996 Mar;270(3 Pt 1):C778-85 PMID: 8638657
  41. Nitric oxide synthase does not participate in negative inotropic effect of acetylcholine in frog heart.
    Am J Physiol. 1996 Apr;270(4 Pt 2):H1178-88 PMID: 8967355
  42. Nitric oxide synthase activity in guinea pig ventricular myocytes is not involved in muscarinic inhibition of cAMP-regulated ion channels.
    Circ Res. 1996 May;78(5):925-35 PMID: 8620613
  43. Adenosine deaminase inhibition prevents free radical-mediated injury in the postischemic heart.
    J Biol Chem. 1996 Apr 26;271(17):10096-102 PMID: 8626567
  44. Erythro-9-(2-hydroxy-3-nonyl)adenine inhibits cyclic-3',5'-guanosine monophosphate-stimulated phosphodiesterase to reverse hypoxic pulmonary vasoconstriction in the perfused rat lung.
    J Pharmacol Exp Ther. 1996 Feb;276(2):752-7 PMID: 8632346
  45. Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells.
    Circ Res. 1996 Jun;78(6):998-1008 PMID: 8635250
  46. Enzyme inhibitors. 26. Bridging hydrophobic and hydrophilic regions on adenosine deaminase with some 9-(2-hydroxy-3-alkyl)adenines.
    J Med Chem. 1974 Jan;17(1):6-8 PMID: 4808472
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119460
Published
1997-06-01
Pages
2710-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508117
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI119460 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2