ABSTRACT
In the lung, b2AR are localized on airway epithelium, airway smooth muscle, alveolar walls, pulmonary vasculature, and resident and transitory immune
cells (2). Clearly relevant to asthma, is the presence of these receptors on
airway smooth muscle, where activation evokes relaxation of bronchi that
are constricted by virtually any stimuli. Also likely relevant to asthma is
epithelial expression where fluid and electrolytic flux and ciliary beat fre-
quency is, in part, regulated by b2AR. Like other members of the G-protein coupled receptor superfamily, the b2AR (a member of the large ‘‘A group’’ of receptors) is a membrane bound receptor with its amino-terminus on the
exterior of the cell, its carboxy-terminus on the interior, and seven transmem-
brane spanning (TMS) domains which appear to be a-helices (Fig. 1). Connecting each TMS domain are extracellular and intracellular loops as
shown, with a ‘‘fourth’’ loop localized in the cell beginning at the carboxy-
terminus of the seventh TMS domain and terminating at a membrane
anchoring palmitoylated cysteine. The receptor has three N-linked glycosylation sites: two in the amino-terminus, and one in the second extracellular
loop of the receptor, the latter found only in higher order primates (3).
Ligand binding (agonist or antagonist) occurs via interactions at specific
amino acids in the ‘‘core’’ of the TMS domains. Signaling to the cell interior
involves coupling to a G-protein (classically the stimulatory G-protein, Gs)
which then acts on effectors such as adenylyl cyclase. b2AR-G-protein interaction occurs in the cell interior, at intracellular TMS domains 2, 3 and part
of the carboxy-tail. In the above scenario, then, b-agonist activation leads to activation of adenylyl cyclase, which converts adenosine tri phosphate to
cyclic adenosine mono phosphate (cAMP), the latter activating protein
Figure 1 Pictorial representation of the b2-adrenergic receptors. The extracellular loops, intracellular loops and the a-helices of the transmembrane spanning domains are shown. The approximate location, and the alleles, of the human polymorphisms are indicated.
