Do low-affinity states of beta-adrenoceptors have roles in physiology and medicine?
The pharmacology once ascribed to the 'beta4-adrenoceptor' is now believed to be that of a low-affinity state of the beta1-adrenoceptor. The beta2-adrenoceptor may also have a low-affinity state or site, while the beta3-adrenoceptor--the original low-affinity beta-adrenoceptor--can display more than one pharmacology. In this issue, Mallem et al. show that CGP-12177 relaxes thoracic aorta rings from normal rats by stimulating vascular smooth muscle low-affinity beta1-adrenoceptors, apparently linked in part to Gi protein. By contrast, in rings from hypertensive rats, CGP-12177 acts mainly via endothelial beta3-adrenoceptors. This work raises the possibility that low-affinity states of beta-adrenoceptors have physiological roles, and suggests that they might be drug targets.
Arch
Jonathan R S
JR
Clore Laboratory for Life Sciences, University of Buckingham, Buckingham, Bucks MK18 1EG. jon.arch@buckingham.ac.uk
D001013:Aorta, Thoracic / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C033394:CGP 12177