Neuropeptide Y inhibits acetylcholine release in human heart atrium by activation of Y2-receptors.
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 [(3)H]-choline to label cholinergic transmitter stores and placed in superfusion chambers. Electrical field stimulations (S1, S2) induced a tetrodotoxin-dependent [(3)H]-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 micromol/l) concentration dependently inhibited acetylcholine release. This effect was prevented by the NPY-Y(2)-receptor antagonist BIIE 0246 (0.1 micromol/l) but not by the NPY-Y(1)-receptor antagonist BIBP 3226 (10 micromol/l). ATP (10 micromol/l), a stable analogue ADP-beta S (3 micromol/l), and NE (1 micromol/l) had no effect on acetylcholine release. m-RNA for the NPY-receptor subtypes Y(1), Y(2), Y(4), Y(5), and y(6) 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 Y(2)-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.
Schwertfeger
Eckhard
E
Department of Internal Medicine IV, University Hospital Freiburg, Freiburg, Germany.
Klein
Thomas
T
Vonend
Oliver
O
Oberhauser
Vitus
V
Stegbauer
Johannes
J
Rump
Lars Christian
LC
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020517:Atrial Appendage / Q000187:drug effects* / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006333:Heart Failure / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000097:blood / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000378:metabolism*
D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014665:Vasodilator Agents; D001120:Arginine; C403256:BIIE 0246; D000109:Acetylcholine