Absence of receptor reserve at striatal dopamine receptors regulating cholinergic neuronal activity.
N-propylnorapomorphine (NPA) dose dependently increased rat striatal ACh levels (ED50 = 18 micrograms/kg). After irreversible dopamine (DA) receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), neither the ED50 nor the slope of the dose-response curve for NPA was altered, whereas the maximal response was reduced to 56% of control. Analysis of the results yielded a linear relationship between receptor occupancy and response (i.e. no receptor reserve). In contrast, DA autoreceptors display a large receptor reserve for NPA. The results support the hypothesis that a differential receptor reserve at pre- vs. postsynaptic DA receptors in rat striatum accounts for the autoreceptor selectivity of DA agonists.
Meller
E
E
Millhauser Laboratories and Department of Psychiatry, New York University School of Medicine, NY 10016.
Enz
A
A
Goldstein
M
M
D000109:Acetylcholine / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000978:Antiparkinson Agents; D011804:Quinolines; D011954:Receptors, Dopamine; C009074:N-n-propylnorapomorphine; C000470:EEDQ; D001058:Apomorphine; D002794:Choline; D000109:Acetylcholine