Farm Animal Metabolism and Nutrition

protein-coupled receptor family that has

a characteristic seven transmembrane

domain structure (Fig. 4.7). To date, the

presence of three unique receptors has

been confirmed with the cloning of the


1-, 
2- and 
3-adrenergic receptor genes

in several species (Table 4.7). Homology

among the receptor subtypes is relatively

low (30–50%), with conserved amino

acids primarily restricted to the seven

transmembrane domain segments and

membrane-proximal regions of the intra-

cellular loops (Fig. 4.7). Despite these

differences among receptor subtypes,

amino acid sequences of individual sub-

types are highly conserved across species.

For example, the 
3-adrenergic receptor

is 80–90% conserved across human,

mouse, rat, canine and bovine amino acid

sequences (see Table 4.7 for references).

The transmembrane domains of the 
-

adrenergic receptors have been implicated

in receptor subtype-specific ligand binding.

A series of 
1–
2-adrenergic receptor

chimeras was produced by Marullo et al.

(1995) to study the role of the trans-

membrane domains in ligand binding.

These authors concluded that receptor

specificity is determined by unique inter-

actions among agonists and several trans-

membrane domains. More recently,

individual transmembrane domains of the


1- and 
2-adrenergic receptors were

exchanged to evaluate the role of each

domain individually (Kikkawa et al., 1998;

Kurose et al., 1998). Transmembrane

domains 2 and 7 were implicated in

affinity for the 
2-adrenergic receptor,

while transmembrane domain 2 was

critical for 
1-adrenergic receptor affinity.

Phenethanolamine Repartitioning Agents 79

Fig. 4.7.Primary structure of the 
1-adrenergic receptor. The amino acid sequence of the human 
1-

adrenergic receptor is represented by the one-letter code for amino acids. The polypeptide chain is arranged

according to the model for rhodopsin. Shaded amino acids are conserved across the human 
1-, 
2- and


3-adrenergic receptors (31% of residues). Amino acids in circles are conserved across the 
1-adrenergic

receptor of humans, pigs and sheep (80% of residues; see Table 4.7 for references). Transmembrane domains

are labelled in parentheses.

RLQT

AIA

IV

N L

G V

LV

W

T

N

F

LS

A

ADL

MV

GL V

PV

A

G

CE

TW

S

DV

VCL

TA

EIS

TL

C

A

RD

Y

A

T

P Y

L

T

AR

WV

S

SE

R

Y

V

IP

V

LP

SV

SS

F

A

Q

RR

F

FY

W

M

N

A

C C

C

F

F

E

R

Y

L

L

MI

F

N

P

WCL

L

L

N

NW

A

F

G

G T

T

G

L

E

L G N F P Y C F

I

RS

S

P R A

Y

D F

LLC

FR

04 Farm Animal Metabolism 04 20/4/00 12:02 pm Page 79