Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons.
Acetylcholine can be released from parasympathetic nerve endings in rat atria by 57 mM K+ depolarization or by electrical field stimulation. We have studied the presynaptic modulation of [3H]acetylcholine release from superfused rat atria prelabeled with [3H]choline. Exogenous acetylcholine and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]acetylcholine into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 microM. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]acetylcholine overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]acetylcholine. These data suggest that acetylcholine release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]acetylcholine by approximately 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 microM, respectively. The inhibitory effect of norepinephrine is blocked by the alpha-adrenergic receptor antagonist yohimbine but not by the beta-adrenergic receptor antagonist propranolol. We suggest that presynaptic muscarinic and alpha-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.
Wetzel
G T
GT
Brown
J H
JH
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000378:metabolism*; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*
D018377:Neurotransmitter Agents; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D013566:Sympathomimetics; D009388:Neostigmine; D001285:Atropine; D000109:Acetylcholine; D011188:Potassium