ABSTRACT
Phosphorylation and dephosphorylation are major biochemical mechanisms to regulate the function of many cellular proteins. The major known components of the adrenergic coupled, dually regulated adenylate cyclase are the stimulatory receptors, like the β-adrenergic receptors, the inhibitory receptor, like the α2-adrenergic or muscarinic receptor, and finally the catalytic unit of the adenylate cyclase. All these components have been purified, and most of them have been cloned and sequenced. The β-adrenergic receptor is the only receptor stimulatory to the adenylate cyclase which has been purified. Tachyphylaxis, or desensitization to hormonal stimulation, significantly limits the clinical and therapeutical use of many hormones and drugs. Heterologous desensitization by incubation with a hormone or drug leads to a general blunting of the adenylate cyclase response. Evidence for sequestration and internalization of the receptor as a very rapid and effective mechanism in homologous desensitization has come initially from many cell fractionation experiments.
