Insights into GPCR pharmacology from the measurement of changes in intracellular cyclic AMP; advantages and pitfalls of differing methodologies.
It is clear that the G protein-coupled receptor family play a key role in the pharmaceutical industry, with a significant proportion of approved drugs targeting this protein class. While our growing understanding of the complexity of G protein-coupled receptor pharmacology is playing a key role in the future success of these endeavours, with allosteric mechanisms now well integrated into the industrial community and G protein-independent signalling mechanisms establishing themselves as novel phenomenon to be exploited, it is still possible to underestimate the complexity of G protein signal transduction mechanisms and the impact that inappropriate study of these mechanisms can have on data interpretation. In this manuscript we review different approaches to measuring the cAMP signal transduction pathway, with particular emphasis on key parameters influencing the data quality and biological relevance.
Institute of Cell Signalling, School of Biomedical Sciences, Medical School, Queen's Medical Centre, Nottingham, UK. Stephen.Hill@nottingham.ac.uk
Stephen J
SJ
Hill
Christine
C
Williams
Lauren T
LT
May
D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D000242:Cyclic AMP / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D011955:Receptors, Drug; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP