Expression and characterization of the porcine beta 2-adrenergic receptor and tissue distribution of beta-adrenergic receptor subtypes in pigs

Wei Liang, Purdue University

Abstract

Stimulation of the β-adrenergic receptor (βAR) system by administration of synthetic β-adrenergic agonists (βAA) is effective in increasing the proportion of muscle to fat in growing livestock. Pigs, however, have a limited response to the commonly used βAA. In order to determine if the porcine β2AR (pβ2AR) accounts for the species specificity, the pβ2AR gene was cloned and stably transfected into Chinese hamster ovary (CHO) cells. The expressed pβ2AR exhibited characteristic features of β2AR. However, some species-specific characteristics of the pβ2AR were observed. ICI 118,551, a strong β2-selective antagonist in most species, was non-selective toward porcine β1AR and β2AR. BRL 37344, a β3AR selective agonist, exhibited high selectivity for the pβ2AR but little or no agonist activity. Clenbuterol and ractopamine were full agonists toward β2AR from human and rat. In contrast, they were weak agonists toward the pβ2AR. These species specific characteristics of the pβ2AR are consistent with the unique features of porcine cells and tissues in binding and response to the stimulation of βAA. We conclude that the species specificity of the pβ2AR in ligand binding and signaling may largely contribute to the lack of response of pigs to the stimulation of many purported β2AA. βA subtypes in pig tissues were quantified using ligand binding with CGP 20712A and BRL 37344 as β1AR and β2AR selective ligands respectively. Multiple βAR subtypes were present in all five tissues and likely represented almost solely by β1AR and β2AR. The proportion of the β1AR and β2AR were 81:19, 59:41, 72:28, 58:42 and 50:50 for the adipocytes, skeletal muscle, heart, lung and liver respectively. These ratios differ from estimates in other species. The predominance of β1AR in the adipose tissue and skeletal muscle may contribute to the reduced efficacy of βAA in pigs, compared to other species because most of the tested ligands are purported to be β2AA.

Degree

Ph.D.

Advisors

Mills, Purdue University.

Subject Area

Pharmacology|Livestock|Anatomy & physiology|Animals

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