Differential sensitivity of 3H-agonist binding to pre- and postsynaptic 5-HT1A receptors in bovine brain.

1. The full and weak partial 5-HT1A agonist ligands 3H]-8-OH-DPAT and 3H]-BMY-7378 were used to characterize the binding parameters of pre- and postsynaptic 5-HT1A binding sites in bovine dorsal raphe and hippocampal membranes, respectively. The Kd and Bmax values for the individual radioligands were indistinguisable across the regions tested, as were the Ki values generated by a series of agents acting at 5-hydroxytryptamine (5-HT) receptors. 2. The concentration-dependent allosteric attenuation of 3H]-8-OH-DPAT and 3H]-BMY-7378 binding produced by the nonhydrolyzable guanyl nucleotide, Gpp(NH)p, generated similar IC50 values within a particular region; however, these were significantly different between regions. While the maximal attenuation of 3H]-8-OH-DPAT and 3H]-BMY-7378 binding was similar in dorsal raphe, Gpp(NH)p produced a significantly greater attenuation of 3H]-8-OH-DPAT binding in hippocampal membranes when compared to 3H]-BMY-7378. The maximal attenuation of 3H]-8-OH-DPAT binding by Gpp(NHp) in hippocampus was also significantly greater than that seen with either radioligand in dorsal raphe. 3. Although exposure to Gpp(NH)p had no effect on the affinity constants of either radioligand in either region, it produced a concentration-dependent reduction in the maximal number of binding sites for both radioligands in both regions. While the percentage reduction in Bmax values were similar for both radioligands in the dorsal raphe, Gpp(NH)p reduced the Bmax of 3H]-8-OH-DPAT in hippocampus significantly more than that of 3H]-BMY-7378. 4.(ABSTRACT TRUNCATED AT 250 WORDS)