β-Adrenergic receptor subtypes that mediate ractopamine stimulation of lipolysis1,2

Ractopamine HCl is an β-adrenergic receptor (βAR) ligand that was recently approved for use in swine to enhance carcass leanness. The RR stereoisomer of ractopamine is the most active of the four stereoisomers exhibiting the highest affinity and signaling response. The RR isomer exhibits selective activation of the porcine β2AR, which might limit the lipolytic response to ractopamine because the β1AR is the predominant subtype in swine adipocytes and may mediate most of the lipolytic response. Therefore, we determined the βAR subtypes that mediate the lipolytic response to ractopamine in swine adipocytes. In order to confirm the predominant role of the β1AR in porcine adipocytes, isoproterenol-stimulated lipolysis was inhibited by increasing doses of subtype-selective antagonists. Inhibition curves were biphasic using β1AR antagonists (CGP 20712A and bisoprolol) and curve analysis indicated that both β1AR and β2AR contributed to lipolysis with 50 to 60% of the response coming from the β1AR. Inhibition with the β2AR antagonist clenbuterol revealed only one class of βAR that closely approximated the kinetics