TY - JOUR
T1 - Pleiotropic behavior of 5-HT(2A) and 5-HT(2C) receptor agonists
AU - Berg, K. A.
AU - Maayani, S.
AU - Goldfarb, J.
AU - Clarke, W. P.
PY - 1998
Y1 - 1998
N2 - 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 PLA2-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 PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT(2A) receptor system, all agonists tested had greater relative efficacy for PLA2-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.
AB - 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 PLA2-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 PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT(2A) receptor system, all agonists tested had greater relative efficacy for PLA2-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.
UR - http://www.scopus.com/inward/record.url?scp=0032434460&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.1998.tb10180.x
DO - 10.1111/j.1749-6632.1998.tb10180.x
M3 - Article
C2 - 9928246
AN - SCOPUS:0032434460
VL - 861
SP - 104
EP - 110
JO - Annals of The Lyceum of Natural History of New York
JF - Annals of The Lyceum of Natural History of New York
SN - 0890-6564
ER -