Muscarinic receptors on dopamine terminals in the cat caudate nucleus: neuromodulation of [3H]dopamine release in vitro by endogenous acetylcholine.
The directly acting muscarinic receptor agonist oxotremorine (1.8-10 microM) produced an increase in electrically evoked [3H] dopamine release from slices of the cat caudate. The maximal increase caused by oxotremorine was 40%, and was antagonized by the muscarinic receptor blocking agent atropine (0.1 microM). Exposure to the acetylcholinesterase (AChe) inhibitor physostigmine (1 microM) resulted in a 50% increase in electrically evoked [3H]dopamine release. The increase caused by physostigmine was also antagonized by atropine (0.1 microM). Atropine did not, however, alter the modulations in [3H]dopamine release mediated by the dopamine autoreceptor: the increase in electrically evoked [3H]dopamine release caused by the dopamine receptor antagonist S-sulpiride (0.1 microM) and the decrease caused by the dopamine receptor agonist pergolide (30 nM) were unaffected by atropine (0.1 microM). These results indicate that the muscarinic receptor-mediated and dopamine autoreceptor-mediated presynaptic effects on [3H]dopamine release are independent. The present results suggest that in the electrically depolarized caudate slice in vitro, released endogenous acetylcholine may interact with muscarinic receptors facilitating depolarization-evoked [3H]dopamine release, if AChE is inhibited. These muscarinic receptors may be located on dopamine nerve terminals. In the context of present neuroanatomical knowledge, the action of released endogenous acetylcholine on dopamine terminals may be a non-synaptic neuromodulation.
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D010830:Physostigmine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D010830:Physostigmine; D012601:Scopolamine; D000109:Acetylcholine; D004298:Dopamine