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Differential Coupling of Serotonin 5‐HT 1A and 5‐HT 1B Receptors to Activation of ERK2 and Inhibition of Adenylyl Cyclase in Transfected CHO Cells
Author(s) -
Mendez Jorge,
Kadia Tapan M.,
Somayazula Ravi K.,
ElBadawi Khaled I.,
Cowen Daniel S.
Publication year - 1999
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 - 10.1046/j.1471-4159.1999.0730162.x
Subject(s) - adenylyl cyclase , receptor , 5 ht receptor , forskolin , adcy10 , adcy9 , serotonin , biology , g protein coupled receptor , gs alpha subunit , g protein , protein kinase a , camp dependent pathway , 5 ht2 receptor , endocrinology , medicine , microbiology and biotechnology , kinase , biochemistry
Although the subtypes of serotonin 5‐HT 1 receptors have distinct structure and pharmacology, it has not been clear if they also exhibit differences in coupling to cellular signals. We have sought to compare directly the coupling of 5‐HT 1A and 5‐HT 1B receptors to adenylyl cyclase and to the mitogen‐activated protein kinase ERK2 (extracellular signal‐regulated kinase‐2). We found that 5‐HT 1B receptors couple better to activation of ERK2 and inhibition of adenylyl cyclase than do 5‐HT 1A receptors. 5‐HT stimulated a maximal fourfold increase in ERK2 activity in nontransfected cells that express endogenous 5‐HT 1B receptors at a very low density and a maximal 13‐fold increase in transfected cells expressing 230 fmol of 5‐HT 1B receptor/mg of membrane protein. In contrast, activation of 5‐HT 1A receptors stimulated only a 2.8‐fold maximal activation of ERK2 in transfected cells expressing receptors at 300 fmol/mg of membrane protein but did stimulate a 12‐fold increase in activity in cells expressing receptors at 3,000 fmol/mg of membrane protein. Similarly, 5‐HT 1A , but not 5‐HT 1B , receptors were found to cause significant inhibition of forskolin‐stimulated cyclic AMP accumulation only when expressed at high densities. These findings demonstrate that although both 5‐HT 1A and 5‐HT 1B receptors have been shown to couple to G proteins of the G i class, they exhibit differences in coupling to ERK2 and adenylyl cyclase.