Biochemical evidence for the presence of presynaptic receptors on dopaminergic nerve terminals.
Two compartments of striatal synaptosome dopamine were identified by differential labelling with the isotopic presursors, L-tyrosine and Dopa, and from specific radioactivity measurement. Either, endogenous or exogenous L-tyrosine could provide a source for the dopamine pool synthesised and released in response to K+ depolarization, whereas external DOPA did not enter this pool. Acetylcholine (0.1 mM) in the presence of neostigmine (0.1 mg/ml) increased dopamine turnover as shown by increased formation of [14C] dopamine and [14C] DOPAC from [14C] DOPA. Haloperidol (0.65 mM) did not affect the size of dopamine pools but increased the conversion of [14C] DOPA to [14C] dopamine and the formation of [14C] DOPAC. Acetylcholine stimulated the release of dopamine from synaptosomes, which effect could be modified by both muscarinic and nicotinic antagonists. In the presence of the muscarinic antagonist, atropine, acetylcholine stimulated dopamine release, whereas in the presence of the nicotinic antagonists, hexamethonium (0.2 mM) or alpha-bungaro-toxin (0.188 muM), acetylcholine inhibited dopamine release. This showed that presynaptic cholinergic receptors were operational, excitatory nicotinic receptors in the former case and inhibitory muscarinic in the latter. The nicotinic receptor was shown to be saturable and to bind specifically 11.2 fmoles of [3H] alpha-bungarotoxin per mg. protein which could be prevented by hexamethonium or D-tubocurarine.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D003342:Corpus Striatum / Q000032:analysis*; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007980:Levodopa / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000032:analysis*; D011978:Receptors, Nicotinic / Q000032:analysis; D012756:Sheep; D013574:Synaptosomes / Q000032:analysis* / Q000187:drug effects; D014443:Tyrosine / Q000494:pharmacology
D002038:Bungarotoxins; D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; D014443:Tyrosine; D007980:Levodopa; D006220:Haloperidol; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine