TY - JOUR
T1 - Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells
AU - Martin, Michael W.
AU - Scott, Allelia W.
AU - Johnston, Douglas E.
AU - Griffin, Suzy
AU - Luedtke, Robert R.
N1 - Funding Information:
The authors are indebted to Dr. Marc Caron of Duke University for providing them with the clones for the rat dopamine D1 and D5 receptors. The authors would also like to thank Ms. Rebekah Freeman for her technical assistance and her assistance in the preparation of this manuscript. This work was supported by grants from the Scottish Rite Schizophrenia Research Program, the National Alliance for Research on Schizophrenia and Depression (NARSAD) and the National Institute of Neurological Disorders and Stroke (NS30507).
PY - 2001/5/25
Y1 - 2001/5/25
N2 - The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, α-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.
AB - The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, α-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.
KW - Adenylyl cyclase stimulation
KW - Antipsychotic
KW - Baculovirus expression
KW - Dopamine D1 receptor
KW - Dopamine receptor
KW - Inverse agonist
UR - http://www.scopus.com/inward/record.url?scp=0035946931&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(01)00982-7
DO - 10.1016/S0014-2999(01)00982-7
M3 - Article
C2 - 11408027
AN - SCOPUS:0035946931
VL - 420
SP - 73
EP - 82
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -