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Homologous Desensitization of the D 1 Dopamine Receptor
Author(s) -
Balmforth Anthony J.,
Warburton Philip,
Ball Stephen G.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb05803.x
Subject(s) - dopamine , endocrinology , agonist , medicine , chemistry , stimulation , forskolin , fenoldopam , desensitization (medicine) , dopamine receptor , receptor , biology
Preincubation of D384 cells, derived from the human astrocytoma cell line G‐CCM, with dopamine resulted in a time‐dependent attenuation of cyclic AMP responsiveness to subsequent dopamine stimulation. This effect was agonist specific because the prostaglandin E 1 (PGE,) stimulation of cyclic AMP of similarly treated cells remained unchanged. The attenuation by dopamine was concentration dependent with a maximum observed at 100 μ M . A comparison of dopamine concentration‐response curves of control and dopamine‐preincubated cells revealed no change in the K a apparent value, but a marked attenuation of the maximal response. Preincubation of cells with dopamine in the presence of D 1 but not D 2 selective antagonists partially prevented the observed attenuation. Attenuations in dopamine responsiveness were also obtained when D384 cells were preincubated with D 1 but not D 2 receptor agonists. The level of attenuation attained related to agonist efficiency in stimulating cyclic AMP: SKF38393 < 3,4‐dihydroxynomifensine < fenoldopam < 2‐amino‐6,7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene = dopamine. However, increasing the efficiency of 3,4‐dihydroxynomifensine stimulation of cyclic AMP, using the synergistic effect of adding a low concentration of forskolin, produced no further change in the attenuation of the subsequent response to dopamine. Thus, the D 1 dopamine receptors expressed by D384 cells undergo homologous desensitization. Uncoupling of the D 1 dopamine receptor appears to be independent of cyclic AMP formation, analogous to a mechanism proposed for the β‐adrenergic receptor.