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Pleiotropic Behavior of 5‐HT 2A and 5‐HT 2C Receptor Agonists
Author(s) -
BERG K. A.,
CLARKE W. P.,
MAAYANI S.,
GOLDFARB J.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10180.x
Subject(s) - agonist , receptor , chemistry , phospholipase c , 5 ht receptor , inositol phosphate , signal transduction , functional selectivity , g protein coupled receptor , microbiology and biotechnology , inositol , pharmacology , serotonin , endocrinology , biology , biochemistry
There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed “agonist‐directed trafficking of receptor stimulus”, that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5‐HT 2A and 5‐HT 2C receptors couple to phospholipase C‐(PLC) mediated inositol phosphate (IP) accumulation and PLA 2 ‐mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5‐HT) differed depending upon whether IP accumulation or AA release was measured. For the 5‐HT 2C receptor system, some agonists ( e.g. TFMPP) preferentially activated the PLC‐IP pathway, whereas others ( e.g. LSD) favored PLA 2 ‐AA. As expected, EC 50 's of agonists did not differ between pathways. For the 5‐HT 2A receptor system, all agonists tested had greater relative efficacy for PLA 2 ‐AA than for PLC‐IP. In contrast, relative efficacies were not different for 5‐HT 2A agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist‐directed trafficking hypothesis.