Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists.
The dose response curve for apomorphine reversal of gamma-butyrolactone (GBL)-induced L-DOPA accumulation in rat striatum was shifted almost 6-fold to the right after partial irreversible blockade (83%) of dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ); however, the maximal response was not reduced. In contrast, the major effect of a similar degree of irreversible blockade (86%) on the dose-response curve for the autoreceptor-selective agent EMD 23,448 was a reduction in maximal response (60% of control), indicating that EMD 23,448 is a partial agonist. A large receptor reserve therefore exists at the DA autoreceptor, which may explain in part why many DA agonists are more potent in models pre- than postsynaptic receptor activation.
Meller
E
E
Helmer-Matyjek
E
E
Bohmaker
K
K
Adler
C H
CH
Friedhoff
A J
AJ
Goldstein
M
M
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*
D007211:Indoles; D011804:Quinolines; D011954:Receptors, Dopamine; D007980:Levodopa; C000470:EEDQ; C037307:3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole; D001058:Apomorphine; D015107:4-Butyrolactone