ArticleBritish journal of pharmacology2003
Inhibition of cyclic GMP hydrolysis with zaprinast reduces basal and cyclic AMP-elevated L-type calcium current in guinea-pig ventricular myocytes.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- G Protein-Coupled Receptor 35 Suppresses Oxidative Stress Responsive Kinase 1 in Diabetic Wound Healing.Diabetes · 2025Article
- Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.Journal of molecular and cellular cardiology · 2017Article
- Inhibition of L-type Ca(2+) current by ginsenoside Rd in rat ventricular myocytes.Journal of ginseng research · 2015Article
- sGC{alpha}1 mediates the negative inotropic effects of NO in cardiac myocytes independent of changes in calcium handling.American journal of physiology. Heart and circulatory physiology · 2011Article
- Identification of cytosolic phosphodiesterases in the erythrocyte: a possible role for PDE5.Medical science monitor : international medical journal of experimental and clinical research · 2011Article
- BNP controls early load-dependent regulation of SERCA through calcineurin.Basic research in cardiology · 2010Article
- Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Initiation of Plasmodium sporozoite motility by albumin is associated with induction of intracellular signalling.International journal for parasitology · 2010Article
- Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes.Journal of molecular and cellular cardiology · 2009Article
- Nitric oxide signaling and the regulation of myocardial function.Journal of molecular and cellular cardiology · 2008Review
- The fork in the nitric oxide road: cyclic GMP or nitrosylation?Nitric oxide : biology and chemistry · 2008Article
- Endothelial nitric oxide synthase decreases beta-adrenergic responsiveness via inhibition of the L-type Ca2+ current.American journal of physiology. Heart and circulatory physiology · 2008Article
- The emerging role for type 5 phosphodiesterase inhibition in heart failure.Current heart failure reports · 2006Review
- Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes.Circulation · 2006Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
(1) Cyclic GMP (cGMP) has been shown to be an important modulator of cardiac contractile function. A major component of cGMP regulation of contractility is cGMP-mediated inhibition of the cardiac calcium current (I(Ca)). An under-appreciated aspect of cyclic nucleotide signalling is hydrolysis of the cyclic nucleotide (i.e., breakdown by phosphodiesterases (PDEs)). The role of cGMP hydrolysis in regulating I(Ca) has not been studied. Thus the purpose of this study was to investigate if inhibition of cGMP hydrolysis can modulate I(Ca) in isolated guinea-pig ventricular myocytes. (2) Zaprinast, a selective inhibitor of cGMP-specific PDE (PDE5), caused a significant increase in cGMP levels in myocytes, but was without affect on basal or beta-adrenergic stimulated cAMP levels (consistent with its actions as a specific inhibitor of PDE5). (3) Zaprinast inhibited I(Ca) that was pre-stimulated with cAMP elevating agents (isoproterenol, a beta-adrenergic agonist; or forskolin, a direct activator of adenylate cyclase). The effect of zaprinast was greatly reduced by KT5823, an inhibitor of cGMP-dependent protein kinase (PKG). (4) Zaprinast also significantly inhibited basal I(Ca) when perforated-patch or whole-cell recording with physiological pipette calcium concentration (10(-7) M) was used. However, this effect was not observed when using standard calcium-free whole-cell recording conditions. (5) These results indicate that inhibition of cGMP hydrolysis can decrease both basal and cAMP-stimulated I(Ca). Thus, cGMP hydrolysis may likely be an important step for physiological modulation of I(Ca). This regulation may also be important in disease states in which cGMP production is increased and PDE5 expression is altered, such as heart failure.
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