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Department of Animal Science, Purdue University, West Lafayette, IN 47907
2 Correspondence: Lilly Hall (phone: 765-494-4845, fax: 765-494-9346; E-mail: smills{at}purdue.edu).
Abstract
The potential for beta-adrenergic receptor (ßAR) agonists to modify growth rate and body composition has been investigated for over 20 yr. Ractopamine was developed by Elanco Animal Health and is the first ßAR ligand to be cleared for use in pigs in the United States, which occurred in 2000. Ractopamine is structurally similar to the natural catecholamines epinephrine and norepinephrine and binds with high affinity to ßAR in pig adipose and muscle tissue. The family of ßAR, however, belongs to a much larger family of structurally related G-protein coupled receptors (GPCR) and there is little or no information available as to whether ractopamine binds and signals through additional GPCR. The question of whether ßARmediate the growth response in pigs and other animals is not fully settled, but primary attention has been given to understanding how ßAR might mediate increased growth and protein accretion, and whether effects are direct on adipose and muscle tissue or mediated by secondary factors. Ractopamine is a racemic mixture of four isomers resulting from two asymmetric carbons. The RR isomer (levorotatory at both carbons) has the highest affinity for the pig ß1AR and ß2AR and Kd values are essentially equivalent for both subtypes (
25 nM). Other isomers have from 3- to 600-fold lower affinity. The RR isomer appears to mediate the growth response in rats and likely is the active isomer in pigs. Therefore, ractopamine can be considered nonselective in binding to either the ß1AR or ß2AR in pigs. It is not known, however, whether the ß3AR or additional subtypes may mediate a ractopamine response. Direct activation of ßAR in adipocytes promotes triglyceride hydrolysis and decreases fatty acid and triglyceride synthesis, thus leading to less lipid accumulation. Fat accretion in pigs given ractopamine is not consistently reduced, which may result from ßAR down-regulation. Ractopamine consistently increases muscle protein accretion in pigs. Responses are maximal within the 1st wk and decline toward zero over 4 to 6 wk. Curiously, ßAR down-regulation is not significant in skeletal muscle. The mechanism responsible for increased protein accretion is not clear, but cumulative evidence points to a direct effect, possibly involving both protein synthesis and degradation.
1 Journal paper no. 16690 of the Purdue Univ. Agric. Res. Prog. Presented in part at the 2001 IAAFSC Mtg. (J. Anim. Sci. 79[Suppl. 1]:238 [Abstr.]).
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