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- Title
Neuropeptide Y inhibits acetylcholine release in human heart atrium by activation of Y<sub>2</sub>-receptors.
- Authors
Schwertfeger, Eckhard; Klein, Thomas; Vonend, Oliver; Oberhauser, Vitus; Stegbauer, Johannes; Rump, Lars Christian
- Abstract
Congestive heart failure and other cardiac diseases are characterized by increased activity of the sympathetic nervous system, whereas at the same time parasympathetic activity is often suppressed. Such imbalance may be a result of or at least enhanced by presynaptic inhibitory effects of sympathetic neurotransmitters on acetylcholine release. We investigated whether the sympathetic cotransmitters neuropeptide Y (NPY), norepinephrine (NE), and ATP are capable of modulating acetylcholine release in human heart atrium. Human atrial appendages were incubated with [3H]-choline to label cholinergic transmitter stores and placed in superfusion chambers. Electrical field stimulations (S1, S2) induced a tetrodotoxin-dependent [3H]-release, which was taken as an index of endogenous acetylcholine release. NE, NPY, ATP, and a P2-receptor analogue were added before S2. NPY (0.05–1.0 μmol/l) concentration dependently inhibited acetylcholine release. This effect was prevented by the NPY-Y2-receptor antagonist BIIE 0246 (0.1 μmol/l) but not by the NPY-Y1-receptor antagonist BIBP 3226 (10 μmol/l). ATP (10 μmol/l), a stable analogue ADP-βS (3 μmol/l), and NE (1 μmol/l) had no effect on acetylcholine release. m-RNA for the NPY-receptor subtypes Y1, Y2, Y4, Y5, and y6 was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). The results suggest that the sympathetic neurotransmitter NPY inhibits parasympathetic neurotransmission in the human heart through activation of presynaptic Y2-receptors. NE and ATP seem not to play a role. Since NPY plasma levels are high in chronic heart failure patients, NPY may be one component leading to impaired parasympathetic neurotransmission in those patients.
- Subjects
HEART diseases; CARDIOVASCULAR diseases; NEUROPEPTIDES; NEUROPEPTIDE Y; ACETYLCHOLINE; HEART atrium
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2004, Vol 369, Issue 5, p455
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-004-0930-9