Farm Animal Metabolism and Nutrition

receptors. Activation of 
-adrenergic

receptors is coupled to Gs proteins

and activation of adenyl cyclase, which

converts adenosine triphosphate (ATP) to

cyclic adenosine monophosphate (cAMP),

an intracellular signalling molecule. The

cAMP is thought to bind the regulatory

subunit of protein kinase A to release its

catalytic subunit. Regulation of intra-

cellular enzymes is then accomplished

through phosphorylation by protein kinase

A (Fig. 4.6).

Activation of 
-adrenergic receptors

and the cAMP signalling pathway by

phenethanolamines results in the activa-

tion of hormone-sensitive lipases and

inactivation of lipogenic enzymes involved

in de novosynthesis of fatty acids and

triglycerides (Fain and Garcia-Sainz, 1983;

Mersmann, 1987). Specific effects of

phenethanolamines on adipose tissue have

been studied in several species. For

example, in vivo adiministration of

ractopamine to swine enhances in vitro

release of free fatty acids and depresses the

activity of lipogenic enzymes in adipose

tissue (Merkel et al., 1987). Ractopamine

also depresses lipogenesis and triacyl-

glycerol synthesis in the adipogenic cell

line TA1 (Dickerson et al., 1988), inhibits

fat cell proliferation of stromalvascular

cells obtained from rat inguinal fat pads

(Jones et al., 1987) and inhibits fat cell

responsiveness to insulin (Williams et

al., 1987; Hausman et al., 1989). Thus,

phenethanolamines have the potential to

increase the rate of lipolysis and decrease

the rate of lipogenesis in adipose tissue via

several mechanisms.

Skeletal muscle

The anabolic effects of phenethanolamines

that result in muscle cell hypertrophy,

muscle fibre type changes (Table 4.5) and

increased lean mass (Beermann et al.,

1986; Maltin et al., 1986; Kim et al., 1987)

are often attributed to activation of the


-adrenergic receptor pathway. However,

Phenethanolamine Repartitioning Agents 75

Fig. 4.6.Mechanism of signal transduction from 
-adrenergic receptors (
AR). The 
-adrenergic receptor is

activated by an agonist and interacts with Gs proteins. The Gs proteins stimulate adenylyl cyclase (AC) to

convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) which acts as an intra-

cellular signalling molecule. Increased levels of cAMP activate protein kinase A (PKA) to phosphorylate

many enzymes and regulatory factors important in metabolic regulation (see text for references).

-Adrenergic agonist

AR

ATP cAMP

PKAinactive PKAactive

Enzyme

phosphorylation

Membrane

AC Gs

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