RECEPTOR “ A receptor is a macromolecular component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to drug's observed effects both desired and undesired”. The latest conceptual definition of receptor is as under: “Receptors are sensing elements in the system of chemical communications that coordinates the function of all the different cells in the body”.

The attachment of drug to a receptor is necessary but not sufficient pre - requisite for pharmacological activity. There are very different types of linkage between the receptor occupation and occurrence of pharmacological response. CLASSIFICATION: Receptors are classified on the basis of molecular structure and the nature of linkage ( the transduction mechanism)

into four types, which are as follows: 1- Ligand - gated ion channels 2- G - Protein - coupled receptors 3- Kinase - linked and related receptors 4- Nuclear receptors 1- Ligand Gated ion Channels:- They are also known as ionotropic receptors. In this type the ion channel runs through the receptor itself. These ion channels opened

When some ligand (Agonist) binds with receptor usually in the extracellular domain. When ligand bind with this ion channel, it permits simultaneous diffusion of Na+ into and K+ out of the post synaptic cell that leads to depolarization or hyperpolarization. These receptors produce effect in millisecond that’s why only fast neurotransmitters act on these type of receptors. e.g. Nicotinic acetylcholine receptor GABAA receptor Glutamate receptors.

2- G-Protein-Coupled Receptors (GPCRs) :- G-protein-coupled receptors are so named because their activity is influenced by guanosine nucleotides (GDP and GTP). They are also called seven-trans membrane spanning (heptahlical) receptors or metabotropic receptors as they structurally cross the plasma membrane seven times. The G-Protein is a membrane protein comprising three subunits (α, β, γ), the α-subunit possessing GTPase activity.

When G-protein binds to receptor, the α-subunit dissociates and becomes free to activate an effector (that may be a membrane enzyme or ion channel). In some cases the β, γ-subunit may be the activator species.

There are two target sites for G-Proteins which are as follows: 1 There are two target sites for G-Proteins which are as follows: 1. Enzyme 2. Ion channel When GPCRs target the enzyme , there is release of second messenger e.g. diacylglycerol (DAC), Cyclic adenosine monophosphate (cAMP), inositol triphosphate (IP3) etc, that transfers the signal of binding agent i.e. (agonist/antagonist) to the effector that produces cellular response.

. GPCRs can control the function of ion channel directly without involving the release of second messengers. e.g. In cardiac muscle, muscarinic (M2) acetylcholine receptors are G-Protein coupled and they enhance the K+ permeability (thus hyperpolarizing the cell and inhibiting electrical activity). Similar mechanism operate in neuron, where opiate analgesics reduce excitability by opening K+ channels.

Examples of GPCRs:- mucarinic acetylcholine receptors receptors for many peptides adrenoceptors dopamine receptors 5-HT receptors opiate receptors etc. The onset time of response through this type of receptors is in seconds.

3- Kinase-Linked and Related Receptors:- They comprise an extracellular lignad binding domain for chemical signals and intracellular domain that is an enzyme whose catalytic activity is regulated by the binding of an extracellular signal. These two domains are linked together by a single transmembrane helix. The great majority of these receptors are Protein Kinases, often tyrosine kinases, that phosphorylate intracellular target proteins, thereby changing the physiological function of the target cell. e.g.

receptors for growth factors receptors for insulin and cytokinase etc. The enzyme link receptors transduce responses in a matter of few minutes to a few hours. 4- Nuclear Receptors:- Nuclear receptors have the ability to directly bind to DNA and regulate the gene transcription. The term nuclear receptor is something of the misnomer because some receptors are actually located in the cytosol and migrate to nuclear compartment when a ligand is present. Receptors are intracellular proteins, so ligands must first enter the cells. e.g. Receptors for steroid hormones

thyroid hormone vitamin D and retinoic acid certain lipid-lowering agent antidiabetic drugs In this type of receptors the onset time of response is very slow and it takes hours.