Are Caenorhabditis elegans receptors useful targets for drug discovery: pharmacological comparison of tyramine receptors with high identity from C. elegans (TYRA-2) and Brugia malayi (Bm4).

ABSTRACT: The biogenic amine, tyramine (TA), modulates a number of key processes in nematodes and a number of TA-specific receptors have been identified. In the present study, we have identified a putative TA receptor (Bm4) in the recently completed Brugia malayi genome and compared its pharmacology to its putative Caenorhabditis elegans orthologue, TYRA-2, under identical expression and assay conditions. TYRA-2 and Bm4 are the most closely related C. elegans and B. malayi BA receptors and differ by only 14aa in the TM regions directly involved in ligand binding. Membranes from HEK-293 cells stably expressing Bm4 exhibited specific, saturable, high affinity, [(3)H]LSD and [(3)H]TA binding with K(d)s of 18.1+/-0.93 and 15.1+/-0.2 nM, respectively. More importantly, both TYRA-2 and Bm4 TA exhibited si

SUBMITTER: Smith KA 

PROVIDER: S-EPMC3430142 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature