Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).
For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.
Backstrom
J R
JR
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6600, USA.
Chang
M S
MS
Chu
H
H
Niswender
C M
CM
Sanders-Bush
E
E
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D051379:Mice; D010716:Phosphatidylinositols / Q000502:physiology; D017393:RNA Editing; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D016415:Sequence Alignment; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015398:Signal Transduction; D014162:Transfection
D010716:Phosphatidylinositols; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D008238:Lysergic Acid Diethylamide