the past decade, receptor cloning and sequencing has greatly facilitated clarification of
this confusing picture. The large number of 5-HT receptors may be divided into five
subtype families. The 5 - HT 1 familycontains receptors that are negatively coupled to
adenyl cyclase through a G-protein and includes the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E,
and 5-HT1Freceptors. Biochemical and pharmacological data suggest that the 5-HT1B
receptor, found in rats and mice, and the 5-HT1Dreceptor, found in humans and other
species, are functionally equivalent species homologs. This story is made even more
confusing by the discovery of two genes that encode the human 5-HT1Dreceptor, des-
ignated 5-HT1Dαand 5-HT1Dβ. The 5 - HT 2 familystimulates phosphoinositide-specific
phospholipase C (PI-PLC) and includes the 5-HT2A, 5-HT2B, and 5-HT2C(formerly des-
ignated the 5-HT1C) receptors. Activation of 5-HT2Areceptors also mediates neuronal
depolarization, a result of the closing of potassium channels. To date, the 5 - HT 3 family
is homomeric, consisting of only one subtype protein. This receptor belongs to a
ligand-gated ion channel superfamily; subunits of the 5-HT 3 receptor exhibit sequence
similarity to the nicotinic acetylcholine and GABAAreceptors. The 5-HT 3 receptor is a
serotonin-gated cation channel that causes rapid depolarization of neurons by a tran-
sient inward ion current that is mediated by the opening of a transmembrane ion chan-
nel protein for cations. The 5-HT 3 receptor, like other proteins in the ligand-gated ion
channel superfamily, possesses pharmacological binding sites for alcohols and anes-
thetic agents. The 5 - HT 4 , 5 - HT 6 ,and 5-HT 7 familyincludes receptors coupled to the
stimulation of adenylyl cyclase—an effect opposite to that of the 5-HT 1 family. Two rat
5-HT 7 receptor clones, differing only in the C-terminus amino acid sequence, have been
NEUROTRANSMITTERS AND THEIR RECEPTORS 251Figure 4.9Biosynthesis and degradation of serotonin.