%0 Journal Article %A J Chamberlain %A S J Offord %A B B Wolfe %A L S Tyau %A H L Wang %A A Frazer %T Potency of 5-hydroxytryptamine1a agonists to inhibit adenylyl cyclase activity is a function of affinity for the "low-affinity" state of [3H]8-hydroxy-N,N-dipropylaminotetralin ([3H]8-OH-DPAT) binding. %D 1993 %J Journal of Pharmacology and Experimental Therapeutics %P 618-625 %V 266 %N 2 %X In this study, the radiolabeled 5-hydroxytryptamine1A agonist, [3H]8-hydroxy-N,N-dipropylamino tetralin ([3H]8-OH-DPAT), was shown to have both a high (Kd, 0.7 +/- 0.2 nM) and a low (Kd, 17 +/- 4 nM) affinity binding component in rat hippocampal homogenate preparations in the absence of guanine nucleotides. The high-affinity binding component was markedly reduced by the elimination of Mg++ from the incubation medium and the addition of both the nonhydrolyzable guanine nucleotide guanylylimidodiphosphate (Gpp(NH)p) (100 microM) and 1.0 mM EDTA to the incubation medium. Under these latter conditions, a single binding affinity component was observed with a Kd of 11 +/- 1 nM, a value in good agreement with the value for the low-affinity component measured in the absence of Gpp(NH)p. Further, the Bmax value for the single low-affinity binding component measured in the presence of Gpp(NH)p was essentially equivalent to the total of the two Bmax values found in the absence of Gpp(NH)p. A binding assay was developed using 15 nM [3H]8-OH-DPAT to determine the affinities of serotonergic drugs for the low-affinity component of [3H]8-OH-DPAT binding and these values were compared with their affinities for the high-affinity binding component as well as their potencies in a hippocampal adenylyl cyclase assay. For agonists, the Ki value for the high-affinity binding component was always less than the low-affinity Ki value, whereas the antagonist spiperone had similar values for both the high-affinity and low-affinity binding components.(ABSTRACT TRUNCATED AT 250 WORDS) %U https://jpet.aspetjournals.org/content/jpet/266/2/618.full.pdf