Amiodarone and its putative metabolites fail to activate wild type hTAAR1.
The ability of amiodarone and its putative metabolites to activate unmodified human trace amine associated receptor 1 (hTAAR1) stably expressed in CHO cell lines was evaluated. Receptor activation was monitored by measuring the accumulation of cAMP, the putative hTAAR1 native second messenger, or calcium mobilization in cells where the receptor was coupled to the promiscuous Gq, Galpha16. Despite literature reports of activation of rodent TAAR1 by these agents, no response was seen in either cell line although robust activation was obtained with the endogenous ligand beta-phenethylamine. These results indicate that TAAR1 activation by amiodarone and its analogs is species specific.
Lewin
Anita H
AH
Center for Organic and Medicinal Chemistry, RTI International, PO Box 12194, Research Triangle Park, NC 27709, USA. ahl@rti.org
Navarro
Hernán A
HA
Gilmour
Brian P
BP
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014162:Transfection; D000095383:Trace Amine-Associated Receptors
D000638:Amiodarone; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors