Agonist efficacy and receptor desensitization: from partial truths to a fuller picture.

摘要: It has been demonstrated that the degree of agonist-induced desensitization β2-adrenoceptor is related to agonist efficacy (strength signalling), whereby high-efficacy agonists (e.g. formoterol) cause more phosphorylation and internalization receptor than low-efficacy salmeterol). These early studies, however, used a protocol where were matched for occupancy rather functional effect. In this issue BJP, Duringer colleagues have extended these studies compare ability at equi-effective (cAMP signalling) concentrations equal occupancy. Their data conclusions are quite different from those previously described. After prolonged exposure, all caused similar desensitization, whereas pulse uncovered greater loss responsiveness with ligands. This consistent notion ‘spare receptors’, therefore less sensitive receptors through desensitization. also reflects experience in clinic, both formoterol salmeterol show decline bronchoprotection, after which their effects remain stable. findings challenge ligands always