DIFFERENTIAL SENSITIVITY OF H-3 AGONIST BINDING TO PRESYNAPTIC AND POSTSYNAPTIC 5-HT1A RECEPTORS IN BOVINE BRAIN

1 The full and weak partial 5-HT1A agonist ligands [H-3]-8-OH-DPAT and [H-3]-BMY-7378 were used to characterize the binding parameters of pr e- and postsynaptic 5-HT1A binding sites in bovine dorsal raphe and hi ppocampal membranes, respectively. The K-d and B-max values for the in dividual radioligands were indistinguisable across the regions tested, as were the K-i values generated by a series of agents acting at 5-hy droxytryptamine (5-HT) receptors. 2 The concentration-dependent allost eric attenuation of [H-3]-8-OH-DPAT and [H-3]-BMY-7378 binding produce d by the nonhydrolyzable guanyl nucleotide, Gpp(NH)p, generated simila r IC50 values within a particular region; however, these were signific antly different between regions. While the maximal attenuation of [H-3 ]-8-OH-DPAT and [H-3]-BMY-7378 binding was similar in dorsal raphe, Gp p(NH)p produced a significantly greater attenuation of [H-3]-8-OH-DPAT binding in hippocampal membranes when compared to [H-3]-BMY-7378. The maximal attentuation of [H-3]-8-OH-DPAT binding by Gpp(NHp) in hippoc ampus was also significantly greater than that seen with either radiol igand in dorsal raphe. 3 Although exposure to Gpp(NH)p had no effect o n the affinity constants of either radioligand in either region, it pr oduced a concentration-dependent reduction in the maximal number of bi nding sites for both radioligands in both regions. While the percentag e reduction in B-max, values were similar for both radioligands in the dorsal raphe, Gpp(NH)p reduced the B-max of [H-3]-8-OH-DPAT in hippoc ampus significantly more than that of [H-3]-BMY-7378. 4 These results suggest that while pre- and postsynaptic 5-HT1A receptors may share si milar pharmacological recognition properties, a region-dependent diffe rence in the coupling of the 5-HT1A receptor to G-proteins may exist.