Abstract
We tested the hypothesis that natriuretic peptide receptors (NPRs) that are coupled to cGMP production act in a similar way to nitric oxide (NO) by enhancing acetylcholine release and vagal-induced bradycardia. The effects of enzyme inhibitors and channel blockers on the action of atrial natriuretic peptide (ANP), brain-derived natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were evaluated in isolated guinea pig atrial-right vagal nerve preparations. RT-PCR confirmed the presence NPR B and A receptor mRNA in guinea pig sinoatrial node tissue. BNP and CNP significantly (P < 0.05) enhanced the heart rate (HR) response to vagal nerve stimulation. CNP had no effect on the HR response to carbamylcholine and facilitated the release of [(3)H]acetylcholine during atrial field stimulation. The particulate guanylyl cyclase-coupled receptor antagonist HS-142-1, the phosphodiesterase 3 inhibitor milrinone, the protein kinase A inhibitor H89, and the N-type calcium channel blocker omega-conotoxin all blocked the effect of CNP on vagal-induced bradycardia. Like NO, BNP and CNP facilitate vagal neurotransmission and bradycardia. This may occur via a cGMP-PDE3-dependent pathway increasing cAMP-PKA-dependent phosphorylation of presynaptic N-type calcium channels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacokinetics
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Animals
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Atrial Natriuretic Factor / metabolism*
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Atrial Natriuretic Factor / pharmacology
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Bradycardia / metabolism*
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Calcium Channel Blockers / pharmacology
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Carbachol / pharmacology
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Cardiotonic Agents / pharmacology
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Cyclic GMP / metabolism*
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Enzyme Inhibitors
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Female
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Gene Expression / physiology
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Guanylate Cyclase / genetics
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Guinea Pigs
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Heart Rate / drug effects
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Heart Rate / physiology
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Isoquinolines / pharmacology
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Milrinone / pharmacology
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Natriuretic Peptide, Brain / metabolism
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Natriuretic Peptide, Brain / pharmacology
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Natriuretic Peptide, C-Type / metabolism
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Natriuretic Peptide, C-Type / pharmacology
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Nitric Oxide / metabolism*
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Phosphodiesterase Inhibitors / pharmacology
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Polysaccharides / pharmacology
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RNA, Messenger / analysis
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Receptors, Atrial Natriuretic Factor / genetics
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Sulfonamides*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Tritium
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Vagus Nerve / physiology*
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omega-Conotoxins / pharmacology
Substances
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Calcium Channel Blockers
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Cardiotonic Agents
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Enzyme Inhibitors
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HS 142-1
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Isoquinolines
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Phosphodiesterase Inhibitors
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Polysaccharides
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RNA, Messenger
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Sulfonamides
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omega-Conotoxins
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Tritium
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Natriuretic Peptide, Brain
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Natriuretic Peptide, C-Type
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Nitric Oxide
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Atrial Natriuretic Factor
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Carbachol
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Guanylate Cyclase
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Receptors, Atrial Natriuretic Factor
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atrial natriuretic factor receptor A
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atrial natriuretic factor receptor B
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Cyclic GMP
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Milrinone
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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Acetylcholine