Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists

Eur J Pharmacol. 1986 Apr 16;123(2):311-4. doi: 10.1016/0014-2999(86)90675-8.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Butyrolactone / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Indoles / pharmacology
  • Levodopa / metabolism
  • Male
  • Quinolines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*

Substances

  • Indoles
  • Quinolines
  • Receptors, Dopamine
  • Levodopa
  • EEDQ
  • 3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole
  • Apomorphine
  • 4-Butyrolactone