Farm Animal Metabolism and Nutrition

At least four of the seven transmembrane

domains have been shown to be essential

for binding to the 
3-adrenergic receptor

using computer modelling, site-directed

mutagenesis and photoaffinity labelling

(Strosberg, 1997). The second and third

intracellular loops of the 
2-adrenergic

receptor are involved in signal transduc-

tion, and similar regions of the third intra-

cellular loop are probably also involved in

interactions that mediate signal transduc-

tion for the 
3-adrenergic receptor (see

Strosberg, 1997).

1- and 
2-adrenergic receptors

Phenethanolamines developed for use in

livestock target the 
1- and 
2-adrenergic

receptors. Agonists of these receptors

have been used in humans for cardiac

inotropic support, the treatment of

asthma, and as uterine relaxants

(Hoffman and Lefkowitz, 1996).

Antagonists of the 
-adrenergic receptors,

or 
-blockers, are used as treatment for

high blood pressure, migraine, cardiac

arrhythmias and myocardial infarction

(Hoffman and Lefkowitz, 1996). In live-

stock, agonists of both the 
1- and 
2-

receptors appear to act as repartitioning

agents that shift energy away from adi-

pose tissue and toward skeletal muscle.

The 
1- and 
2-adrenergic receptors

are expressed in a variety of tissues. The

rat heart and guinea pig trachea have been

considered prototypical tissues for

studying ligand binding to the 
1- and


2-receptors, respectively. Most tissues

contain a mixture of the 
-adrenergic

receptor subtypes with varying densities of

each (Minneman et al., 1979). Expression

of 
-adrenergic receptors has been demon-

strated in adipose and skeletal muscle

tissues of livestock species, but the relative

abundance of different 
-adrenergic

receptor subtypes has not been clearly

defined (see Mersmann, 1998).

Classification of 
-adrenergic

receptor agonists

Classification of subtype selectivity of 
-

adrenergic receptor agonists is based on the

ability of agonists and antagonists to stimu-

late or inhibit a particular physiological–

pharmacological response, or to bind to the

receptor (Mersmann, 1995). 
-Adrenergic

receptor ligands may be classified by their

binding to human and rodent 
-adrenergic

receptors using stably transfected Chinese

hamster ovary (CHO) cells that express a

high copy number of one 
-adrenergic

receptor subtype. These cells may be used to

investigate ligand binding as well as ligand

activity (agonist or antagonist) by measuring

cAMP accumulation. To date, the bovine 
3-

80 D.E. Moody et al.

Table 4.7.The 
1-, 
2- and 
3-adrenergic receptors have been cloned and sequenced in several species.

Accession Numbera

Species 
 1 
 2 
 3

Human J03019 J02960 X72861

Monkey X75540 L38905 U63592

Mouse L10084 X15643 X72862

Rat J05561 X17607 S73473

Cattle AF188187 Z86037 X85961

Pigs AF042454 AF000134 U55858 (fragment)

Sheep AF072433 — —

Dog Huang et al.(1997) Huang et al.(1997) U92468

Turkey bM14379 cU13977 —

aAccession numbers refer to the GenBank nucleotide database (www.ncbi.nlm.nih.gov).

bThe sequence is named the avian 
-adrenergic receptor and is not necessarily the 
1-subtype homologue.

cThe sequence is named the 
4c-adrenergic receptor and is not necessarily the 
2-homologue.

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