PHARMACOLOGY

 G-PROTEINS ::

There is a well organized hierarchy in the effect of a drug produced in a system after it has bound to receptors This is true particularly for Type II receptors The first step in the hierarchy of various metabolic cascade is activation of a specific protein named as G-proteins Thus G-proteins are intermediates between the receptors and the effector system They are also called as metabotropic receptors Their name G- has come because they interact with guanine nucleotides GTP and GDP Each G-protein consists of three subunits a b and y Guanine nucleotide binds to the a subunit and this has enzymatic activity which catalyzes conversion of GTP to GDP The other two subunits b and y remain as a B y complex All the three subunits are anchored to the membrane through a fatty acid chain attached to an aminoacid residue through a reaction called prenylation 

            The coupling of the a-subunit to an agonist -occupied receptor cause the bound GDP to exachange with intracellular GTP The a-GTP complex then dissociates from the receptor and form By complex The dissociated a-GTP then interacts with target protein (Target 1) which may be an enzyme like adenylyl cyclase or phospholipase or an ion channel The by complex may also activate another target protein (Target 2) The GTPase activity of the a -subunit is increased when the target protein is bound This causes hydrolysis of bound GTP

 

    The G-protein consists of three subunits (a.b,y) which are anchored to the membrane through attached lipid residues coupling of the a subunit to an agonist occupied receptor causes the bound GDP to exchange with intracellular GTP complex then dissociates from the receptor and from the BY complex and interacts with a target protein (Target l which may be an enzyme such as adenylate cyclase or an ion channel) The BY complex may also activate a target protein (Target 2) The GTP-ase activity of the a-subunit is increased when the target protein is bound leading to hydrolysis of the bound GTP to GDP where upon the a- subunit reunites with BY 

TO GDP and hence GDP is regenerated and BY subunit reunites with a-subunit The activation of effector is terminated when the GDP is regenerated along with reunion of BY subunit 

        There are several types of G-proteins which interact with different receptors and control different effectors Examples are muscarinic receptors adrenoceptors and neuropeptide receptors There are more than 20 known subtypes of Ga 7 of GB and 12 of Gy providing in theory about 1500 varients of the trimer In general there are three main classes of G-proteins (Gs, G, and Gq) The stimulation and inhibition of adenylyl cyclase occurs through Gs and Gi respectively Similar bidirectional control of phospholipase C occurs through Gs and Gi