Affordable Access

deepdyve-link
Publisher Website

Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1.

Authors
  • Liu, Xuehong
  • Grandy, David K
  • Janowsky, Aaron
Type
Published Article
Journal
Journal of Pharmacology and Experimental Therapeutics
Publisher
American Society for Pharmacology & Experimental Therapeutics
Publication Date
June 2014
Volume
350
Issue
1
Pages
124–129
Identifiers
DOI: 10.1124/jpet.114.213116
PMID: 24799633
Source
Medline
License
Unknown

Abstract

Ractopamine (RAC) is fed to an estimated 80% of all beef, swine, and turkey raised in the United States. It promotes muscle mass development, limits fat deposition, and reduces feed consumption. However, it has several undesirable behavioral side effects in livestock, especially pigs, including restlessness, agitation, excessive oral-facial movements, and aggressive behavior. Numerous in vitro and in vivo studies suggest RAC's physiological actions begin with its stimulation of β1- and β2-adrenergic receptor-mediated signaling in skeletal muscle and adipose tissue; however, the molecular pharmacology of RAC's psychoactive effects is poorly understood. Using human cystic fibrosis transmembrane conductance regulator (hCFTR) chloride channels as a sensor for intracellular cAMP, we found that RAC and p-tyramine (TYR) produced concentration-dependent increases in chloride conductance in oocytes coexpressing hCFTR and mouse trace amine-associated receptor 1 (mTAAR1), which was completely reversed by the trace amine-associated receptor 1 (TAAR1)-selective antagonist EPPTB [N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide]. Oocytes coexpressing hCFTR and the human β2-adrenergic receptor showed no response to RAC or TYR. These studies demonstrate that, contrary to expectations, RAC is not an agonist of the human β2-adrenergic receptor but rather a full agonist for mTAAR1. Since TAAR1-mediated signaling can influence cardiovascular tone and behavior in several animal models, our finding that RAC is a full mTAAR1 agonist supports the idea that this novel mechanism of action influences the physiology and behavior of pigs and other species. These findings should stimulate future studies to characterize the pharmacological, physiological, and behavioral actions of RAC in humans and other species exposed to this drug.

Report this publication

Statistics

Seen <100 times