The Measurement of Cyclic AMP Levels in Biological Preparations

The generation of cyclic AMP (cAMP) is probably the most scrutinized of signal transduction pathways. Receptors may be linked to the generation of AMP by one of two routes. One group of receptors (such as β-adrenoceptors, A₂ adenosine receptors, D₁ dopamine receptors, histamine H₂ receptors, and some of the prostanoid receptors) is associated with an increased adenylyl cyclase activity and elevated cAMP levels mediated through a guanine nucleotide binding protein, G_s . Activation of the second group leads to inhibition of adenylyl cyclase and a reduction in AMP generation. Examples of the latter group include α₂ -adrenoceptors, A₁ adenosine receptors, D₂ dopamine receptors, 5-HT₁ type receptors, metabotropic glutamate receptors, and μ opioid receptors. The mechanism of inhibition of adenylyl cyclase activity appears to be mediated through a distinct guanine nucleotide binding protein, G_i . These two G-proteins act on adenylyl cyclase either to stimulate or inhibit the conversion of ATP to cAMP and PP₁ .