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

Xuehong Liu, David Grandy, Aaron Janowsky

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 ß1- and ß2-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 concentrationdependent 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 ß2-adrenergic receptor showed no response to RAC or TYR. These studies demonstrate that, contrary to expectations, RAC is not an agonist of the human ß2-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.

Original languageEnglish (US)
Pages (from-to)124-129
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume350
Issue number1
DOIs
StatePublished - 2014

Fingerprint

ractopamine
Livestock
Cystic Fibrosis Transmembrane Conductance Regulator
Adrenergic Receptors
Tyramine
Swine
Oocytes
Pharmacology
Psychomotor Agitation
Chloride Channels
Muscle Development
Trace amine-associated receptor 1
Adipose Tissue
Chlorides
Skeletal Muscle
Animal Models
Fats

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1. / Liu, Xuehong; Grandy, David; Janowsky, Aaron.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 350, No. 1, 2014, p. 124-129.

Research output: Contribution to journalArticle

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