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Differential sensitivity of 3 H‐agonist binding to pre‐ and postsynaptic 5‐HT 1A receptors in bovine brain
Author(s) -
Iben Lawrence G.,
Mahle Cathy D.,
Yocca Frank D.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17153.x
Subject(s) - chemistry , radioligand , agonist , dorsal raphe nucleus , postsynaptic potential , allosteric regulation , radioligand assay , receptor , hippocampal formation , medicine , biophysics , endocrinology , biology , serotonin , biochemistry , serotonergic
1 The full and weak partial 5‐HT 1A agonist ligands [ 3 H]‐8‐OH‐DPAT and [ 3 H]‐BMY‐7378 were used to characterize the binding parameters of pre‐ and postsynaptic 5‐HT 1A binding sites in bovine dorsal raphe and hippocampal membranes, respectively. The K d and B max values for the individual radioligands were indistinguisable across the regions tested, as were the K i values generated by a series of agents acting at 5‐hydroxytryptamine (5‐HT) receptors. 2 The concentration‐dependent allosteric attenuation of [ 3 H]‐8‐OH‐DPAT and [ 3 H]‐BMY‐7378 binding produced by the nonhydrolyzable guanyl nucleotide, Gpp(NH)p, generated similar IC 50 values within a particular region; however, these were significantly different between regions. While the maximal attenuation of [ 3 H]‐8‐OH‐DPAT and [ 3 H]‐BMY‐7378 binding was similar in dorsal raphe, Gpp(NH)p produced a significantly greater attenuation of [ 3 H]‐8‐OH‐DPAT binding in hippocampal membranes when compared to [ 3 H]‐BMY–7378. The maximal attentuation of [ 3 H]‐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 B max values were similar for both radioligands in the dorsal raphe, Gpp(NH)p reduced the B max of [ 3 H]‐8‐OH‐DPAT in hippocampus significantly more than that of [ 3 H]‐BMY–7378. 4 These results suggest that while pre‐ and postsynaptic 5‐HT 1A receptors may share similar pharmacological recognition properties, a region‐dependent difference in the coupling of the 5‐HT 1A receptor to G‐proteins may exist.