The effects of kainic acid and 6-hydroxydopamine lesions, metal ions and GTP on in vitro binding of the D-2 dopamine agonist, [3H]N-0437, to striatal membranes.
The kinetic and pharmacological profiles of the potent and selective D-2 dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin ([3H]N-0437) have recently been described. This report concerns the effects of chemical lesions and metal ions on the radioreceptor binding of [3H]N-0437. Kainic acid lesions reduced the maximum number of binding sites (Bmax) in the rat striatum by 50%. The affinity of [3H]N-0437 for dopamine receptors was reduced by half. 6-Hydroxydopamine lesions had no measurable effect on the Bmax or on the KD. Of the physiological metal ions tested only Na+ had a significant effect on the binding. Sodium ions reduced the affinity of [3H]N-0437 for striatal receptors from 5.0 +/- 1.1 nM to 8.4 +/- 0.3 nM. In addition GTP lowered the Bmax from 1121 +/- 44 to 868 +/- 84 fmol/mg protein. The trace ions Li+ and Mn2+ had no effect at a concentration of 3.0 mM, while the exogenous ion Hg2+ at the same concentration prevented the specific binding of [3H]N-0437. Together, the results suggest that [3H]N-0437 labels both pre- and postsynaptic receptors, although postsynaptic receptors are labelled preferentially. Moreover, there is an indication that GTP shifts the affinity state of the D-2 receptor from high to low, while Na+ seems to be an allosteric inhibitor.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008670:Metals / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013563:Sympathectomy, Chemical; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D006892:Hydroxydopamines; D008670:Metals; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D006160:Guanosine Triphosphate; C047508:rotigotine; D016627:Oxidopamine; D007608:Kainic Acid