CHARACTERIZATION OF LIGAND-BINDING PROPERTIES OF THE 5-HT1D RECEPTORSCLONED FROM CHIMPANZEE, GORILLA AND RHESUS-MONKEY IN COMPARISON WITH THOSE FROM THE HUMAN AND GUINEA-PIG RECEPTORS

The 5-HT1D receptor is a potential target of anti-migraine drugs, and here its genes were cloned from chimpanzee, gorilla and rhesus monkey, via polymerase chain reactions with their genomic DNAs and the primer s designed from the 5' and 3' untranslated regions of the human recept or. Direct sequencing of the polymerase chain reaction (PCR) products revealed high degrees of identity between their deduced amino acid seq uences (the chimpanzee, gorilla and rhesus monkey) and that of human, differing by two, four and 11 residues, respectively. The binding prop erties of the receptors, as expressed in human embryonic kidney 293 ce lls, were compared to those obtained with the human and guinea pig rec eptors, the latter differing by 33 residues from the human receptor. S tandard serotonergic ligands including several indoles, ergots and met hiothepin bound all the cloned primate and guinea pig receptors with c omparable, low nanomolar affinities, leading to high correlation coeff icients among their K-i values. R(+)-8-Hydroxydipropylaminotetralin, o n the other hand, bound the human receptor with the affinity higher th an those for the primates and guinea pig receptors. This indicates tha t certain chemical templates may differentiate the molecular divergenc es among the 5-HT1D receptors of various animal species, and the use o f the non-human primates will be beneficial for pharmacological charac terizations, more relevant to the human receptor, of future novel liga nds for the 5-HT1D receptor, which are potential anti-migraine drugs. (C) 1997 Elsevier Science Ireland Ltd.