SUMMARY1. The  -adrenoceptor is currently classified into  1 ,  2 and  3 subtypes and all three subtypes are expressed in smooth muscle. Each  -adrenoceptor subtype exhibits tissue-specific distribution patterns, which may be a determinant controlling the mechanical functions of corresponding smooth muscle. Airway and uterine smooth muscles abundantly express the  2 -adrenoceptor, the physiological significance of which is established as a fundamental regulator of the mechanical activities of these muscles. Recent pharmacomechanical and molecular approaches have revealed roles for the  3 -adrenoceptor in the gastrointestinal tract and urinary bladder smooth muscle.2. The  -adrenoceptor is a G s -protein-coupled receptor and its activation elevates smooth muscle cAMP. A substantial role for a cAMP-dependent mechanism(s) is generally believed to be the key trigger for eliciting  -adrenoceptor-mediated relaxation of smooth muscle. Downstream effectors activated via a cAMP-dependent mechanism(s) include plasma membrane K + channels, such as the large-conductance, Ca 2+ -activated K + (MaxiK) channel. 3.  -Adrenoceptor-mediated relaxant mechanisms also include cAMP-independent signalling pathways. This view is supported by numerous pharmacological and electrophysiological lines of evidence. In airway smooth muscle, direct activation of the MaxiK channel by G s ␣ is a mechanism by which stimulation of  2 -adrenoceptors elicits muscle relaxation independently of the elevation of cAMP.4. The cAMP-independent mechanism(s) is also substantial in  3 -adrenoceptor-mediated relaxation of gastrointestinal tract smooth muscle. However, in the case of the  3 -adrenoceptor, a delayed rectified K + channel rather than the MaxiK channel seems to mediate, in part, cAMP-independent relaxant mechanisms.5. In the present article, we review the distribution of  -adrenoceptor subtypes in smooth muscle tissues and discuss the molecular mechanisms by which each subtype elicits muscle relaxation, focusing on the roles of cAMP and plasma membrane K + channels.
