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Direct activation by dopamine of recombinant human 5‐HT 1A receptors: Comparison with human 5‐HT 2C and 5‐HT 3 receptors
Author(s) -
Oz Murat,
Zhang Li,
Rotondo Alessandro,
Sun Hui,
Morales Marisela
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10273
Subject(s) - receptor , 5 ht receptor , spiperone , xenopus , serotonin , endocrinology , chemistry , medicine , receptor antagonist , antagonist , biology , biochemistry , gene
The effects of dopamine (DA) on the function of human 5‐HT 1A receptors expressed in Xenopus oocytes and CHO‐K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5‐HT receptors (5‐HT 1A , 5‐HT 2C , and 5‐HT 3 ) were studied comparatively in Xenopus oocyte expression system. Application of 5‐HT or DA in oocytes coexpressing 5‐HT 1A receptors and G‐protein‐activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC 50 values of 4.2 nM and 11.2 μM. Maximal responses induced by DA were 85 ± 4% of maximal 5‐HT currents and DA responses were blocked by the specific 5‐HT 1A antagonist, WAY‐100635 (50 nM). In CHO‐K1 cells expressing 5‐HT 1A receptors, 5‐HT and DA inhibited the specific binding of selective antagonist [ 3 H]‐8‐OH‐DPAT with IC 50 values of 10.2 nM and 1.4 μM, and both 5‐HT and DA inhibited the forskolin‐induced accumulation of cAMP. In oocytes expressing 5‐HT 2C receptors, 5‐HT and DA induced inward currents with respective EC 50 values of 6.2 nM and 67.7 μM. Magnitudes of maximal DA induced currents were 42 ± 3% of maximal 5‐HT responses and blocked by the 5‐HT 2 antagonist, piperazine (1 μM). In oocytes expressing 5‐HT 3 receptors, 5‐HT and DA induced fast inward currents with respective EC 50 values of 2.1 μM and 266.3 μM. Maximal DA induced currents were 37 ± 3% of maximal 5‐HT responses and blocked the specific 5‐HT 3 antagonist LY‐278584 (0.1 μM). Comparison of the potencies and efficacies of 5‐HT and DA indicated that the relative potency of DA increased in the order of 5‐HT 3 > 5‐HT 1A > 5‐HT 2C , and relative efficacy increased in the order of 5‐HT 1A > 5‐HT 2C > 5‐HT 3 . These results suggest that although DA activates different subtypes of human 5‐HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors. Synapse 50:303–313, 2003. Published 2003 Wiley‐Liss, Inc.