Muscarinic and dopaminergic receptor subtypes on striatal cholinergic interneurons.
Unilateral stereotaxic injection of small amounts of the cholinotoxin, AF64A, caused minimal nonselective tissue damage and resulted in a significant loss of the presynaptic cholinergic markers [3H]hemicholinium-3 (45% reduction) and choline acetyltransferase (27% reduction). No significant change from control was observed in tyrosine hydroxylase or tryptophan hydroxylase activity; presynaptic neuronal markers for dopamine- and serotonin-containing neurons, respectively. The AF64A lesion resulted in a significant reduction of dopamine D2 receptors as evidenced by a decrease in [3H]sulpiride binding (42% reduction) and decrease of muscarinic non-M1 receptors as shown by a reduction in [3H]QNB binding in the presence of 100 nM pirenzepine (36% reduction). Saturation studies revealed that the change in [3H]sulpiride and [3H]QNB binding was due to a change in Bmax not Kd. Intrastriatal injection of AF64A failed to alter dopamine D1 or muscarinic M1 receptors labeled with [3H]SCH23390 and [3H]pirenzepine, respectively. In addition, no change in [3H]forskolin-labeled adenylate cyclase was observed. These results demonstrate that a subpopulation of muscarinic receptors (non-M1) are presynaptic on cholinergic interneurons (hence, autoreceptors), and a subpopulation of dopamine D2 receptors are postsynaptic on cholinergic interneurons. Furthermore, dopamine D1, muscarinic M1 and [3H]forskolin-labeled adenylate cyclase are not localized to striatal cholinergic interneurons.
Dawson
V L
VL
Neuropsychiatric Research Institute, Fargo, ND 58103.
Dawson
T M
TM
Wamsley
J K
JK
D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013469:Sulpiride / Q000378:metabolism; D014316:Tritium
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D014316:Tritium; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D013469:Sulpiride; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline