A large number of drugs involve G-protein coupled receptor (GCPR) binding. The human body contains thousands of different kinds of GPCR’s and each binds to specific ligands or molecules (Nature Education 2014). So what really are GPCR's?
cAMP Pathway
G-coupled protein receptors are transmembrane receptors passing the cell membrane 7 times (which is labeled as H1 to H7 from above). The N terminus with label NH3 is located at the outer layer of the cell membrane while the C terminus portion can be found intracellularly, labeled as -OOC.
GPCR’s are membrane receptors that usually are found in eukaryotes. These receptors are highly specific where ligands and light sensitive molecules bind resulting to an array of functions in the body. These cell surface receptors contain seven membranes and they relay information to the cell in the absence or presence of life-sustaining light or nutrients depending on the molecule that it attaches. Many drugs act by binding to GPCR’s.
There are three G proteins near the GPCR where it associates into, the alpha, beta, and gamma subunit. Two subunits, the alpha and gamma, are attached by lipid anchors to the plasma membrane. In its inactive state, such as the absence of ligands or molecules specific to the GPCR, the alpha subunit attaches to guanosine diphosphate (GDP) (Nature Education, 2014).
When a ligand binds to GPCR, this seven membrane receptor undergoes a conformational change leading to the attachment of GDP in the alpha subunit G-protein, thus exchanging GDP to guanosine triphosphate (GTP). The alpha subunit then dissociates and attaches to a specific target protein where it regulates. The target protein then relays signals via second messenger and a desired or specific response is achieved. When GTP from the alpha subunit is hydrolyzed to GDP, the ligand moves away from GPCR and the GPCR is ready again for another process where the specific ligand can activate the GPCR pathway (Warne et al, 2008).
Structural knowledge of drug targets like that of GPCR's are essential in drug discovery. Sometimes, scientists have to conduct experiments in changing the structure of a compound to improve drug performance (Dahiya & Mishra, 2007). Drug discovery involves an area called drug development which entails the determination of targets that cause disease. In order to succeed in drug development, areas of drug studies need to be considered such as toxicology, pharmacodynamics and pharmacokinetics (Ng 2004). Being knowledgeable of this can be useful for nurses who would like to engage in clinical research, depending on the area or concentration of study.
References:
Dahiya, K. and Mishra, C. (2007). Drug discovery, development and approval process: Need for an interdisciplinary approach. Pharmacy On-Line. (online). Avalable at: http://www.priory.com/pharmacy/Drug_Discovery.htm
Nature.com (2014) 'GPCR', [online] Available from: http://www.nature.com/scitable/topicpage/gpcr-14047471
Neal, M.J. (2005). Medical Pharmacology at a Glance. Fifth Edition. USA. Blackwell Publishing Ltd.
Pfefforkorn, J.A. et al (2008). Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors. J.Med. Chem. Vol. 51: 35- 45. [online]. Available from: http://www.rcsb.org/pdb/explore/explore.do?structureId=2R4F
Rang, H.P., Dale, M.M., Ritter, J.M., and Moore, P.K. (2003). Pharmacology. Fifth Edition. Philadelphia. Elsvier Science Limited.
Sivakumar, S. (n.d.) cAMP [online]. Available at: http://www.sivabio.50webs.com/amp.htm
Warne, T., Serrano-Vega, M.J., Baker, J., Moukhametzianov, R., Edwards, P., Henderson, R., Leslie, A., Tate, C., and Schertler, G. (2008). Structure of a β1-adrenergic G-protein-coupled receptor. Nature 454, 486-491 [online]. Available at: http://www.nature.com.libezproxy.open.ac.uk/nature/journal/v454/n7203/full/nature07101.html
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