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Molecular biology of the 5‐HT 1 receptor subfamily
Author(s) -
Hartig Paul R.,
Adham Nika,
Zgombick John,
Weinshank Richard,
Branchek Theresa
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430260302
Subject(s) - subfamily , receptor , 5 ht receptor , serotonin , biology , serotonin antagonists , biochemistry , gene
Four serotonin receptor clones have now been isolated and characterized. They encode the serotonin 5‐HT 1A , 5‐HT 1C , 5‐HT 1D , and 5‐HT 2 receptors. The serotonin 5‐HT 1C receptor, which was originally classified as a 5‐HT 1 receptor, is now seen to be a member of the 5‐HT 2 receptor subfamily. Within the current 5‐HT 1 receptor subfamily, the two clones that have been described (5‐HT 1A and 5‐HT 1D ) show similarities in amino acid sequence and function but are not as closely related as might have been expected. The human 5‐HT 1D receptor clone, when expressed in mouse fibroblast cells, displays pharmacological binding properties in agreement with human cortical membrane preparations. Sumatriptan, a new antimigraine medication, exhibits an apparent dissociation constant of 3.4 nM at this human receptor site. This represents the highest affinity interaction yet identified for this drug, and suggests that significant species differences may exist in the binding of this compound to 5‐HT 1D receptors. Similar species differences in ergot drug affinities have been described for the 5‐HT 2 receptor. Deduced amino acid sequence homologies between serotonin and other monoamine receptor clones are discussed, leading to a classification scheme for serotonin receptors involving superfamily, family, and subfamily relationships. © 1992 Wiley‐Liss, Inc.