Abstract
We describe a genomic clone encoding the human 5-HT 1B receptor. This apparently intronless gene encodes a 390 amino acid polypeptide homologous to the rat 5-HT 1B serotonin receptor, with which it shares 93% amino acid sequence identity. Remarkably, [ 3H]5-hydroxytryptamine binding studies with transfected HeLa cells show that the human 5-HT 1B receptor has a pharmacological profile that is markedly different from that of the corresponding rat receptor. Instead, human 5-HT 1B drug specificity is highly similar to that of the human 5-HT 1D receptor, with which it shares 59% amino acid sequence identity. The human 5-HT 1B receptor, like the 5-HT 1D receptor, can couple to Gi proteins. The presence of the threonine 355 in the human receptor rather than an asparagine, as found in the corresponding rat gene product, may explain much of the marked pharmacological difference between the human and rat 5-HT 1B receptors.
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