Naunyn-schmiedebergs Archives of Pharmacology, 2004
Congestive heart failure and other cardiac diseases are characterized by increased activity of th... more 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.
Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, a... more Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence.
Naunyn-schmiedebergs Archives of Pharmacology, 2004
Congestive heart failure and other cardiac diseases are characterized by increased activity of th... more 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.
Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, a... more Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence.
Uploads
Papers by Biie White
Drafts by Biie White