TY - JOUR
T1 - Receptor reserve at striatal dopamine autoreceptors
T2 - Implications for selectivity of dopamine agonists
AU - Meller, E.
AU - Helmer-Matyjek, E.
AU - Bohmaker, K.
AU - Adler, C. H.
AU - Friedhoff, A. J.
AU - Goldstein, M.
N1 - Funding Information:
We thankM s. Judi Scheefro rp reparatioonf t hem anuscript. Supportedb y USPHS GrantsM H-35976,M H-14024,M H-02717M, H-06818a ndN S-06801C. .H. Adlerw ass upporteidn part by NIH Training Grant No. 5T32GM07308fr om the NationaIln stituteos f GeneraMl edicalS ciences.
PY - 1986/4/16
Y1 - 1986/4/16
N2 - The dose response curve for apomorphine reversal of γ-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.
AB - The dose response curve for apomorphine reversal of γ-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.
KW - Apomorphine Receptor receptor reserve EMD 23,448
KW - Dopamine autoreceptors Irreversible receptor inactivation
KW - N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-butyrolactone
UR - http://www.scopus.com/inward/record.url?scp=0022515493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022515493&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(86)90675-8
DO - 10.1016/0014-2999(86)90675-8
M3 - Article
C2 - 3709668
AN - SCOPUS:0022515493
SN - 0014-2999
VL - 123
SP - 311
EP - 314
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -