Receptors are macromolecules which play a vital role in chemical signalling within and between cells. Receptors can be found on the surface of a cell membrane or deep within the cytoplasm. The cellular Biochemical processes are controlled by activated receptors directly or indirectly for example ion conductance, protein phosphorylation, DNA Transcription, and Enzymatic activity.
What Is Ligand?
A ligand is a substance which combines with a biomolecule to form a complex for biological purposes.
Example
In protein-ligand binding, the ligand is a molecule that binds to a target protein which is present on the surface of the receptor and transmits a signal.
Explanation
Ligands are molecules including (Drugs, Hormones, and Neurotransmitters) that bind to a receptor, both selective and reversible binding is possible.
A ligand may activate or inactivate the receptors. Activation may increase or decrease a precise cell function.
Each ligand may interact with multiple receptor subtypes.Few drugs are absolutely specific for one receptor or subtype,but the majority have relative selectivity.Selectivity refers to how well a drug works on a certain site compared to other sites.
What Is Drug-Receptor Complex
A drug receptor is a specialized target macromolecule that binds to a drug and mediates its pharmacological action.These receptors may be Enzymes, Nucleic Acids, or Specialized membrane-bound proteins. The formation of the Drug-Receptor complex results in a Biological Response.
Explanation
The heart contains two types of receptor one is adrenergic and 2nd is cholinergic receptor.
Epinephrene & norepinephrine act on adrenergic receptors & give effect on heart cells.
Acetylcholine acts on Muscarinic receptors.
These two receptors dynamically associate to control the heart's vital functions.The number of drug-receptor complexes directly relates to the significance of the Cellular response.
This concept is similar to the development of a Complex between Enzyme and Substrate and shares common features such as the Specificity of the Receptor for a given Agonist.
What Is an Agonist?
An Agonist is a chemical which activates the receptors to produce the biological response. Agonists increase the proportion of activated receptors e.g Acetylcholine, Norepinephrine, and drugs (e.g, Isoproterenol) act as Agonists.
What Is an Antagonist?
The antagonist is a type of receptor or ligand that blocks a biological response by binding to and blocking a receptor rather than activating it like an agonist. e.g Alpha Blockers, or Beta Blockers.
Partial Agonist Definition
A partial Agonist is an Agonist which is unable to induce maximal activation of a receptor, regardless of the amount of drug applied (e.g. Butorphanol).
Receptor States
The receptor exists in two interchangeable states which are given below,
Ra (active)
Ri (inactive)
These two states are in equilibrium.
Explanation
Receptors exist in around two states, inactive (R) and active (R*), which are reversible and compatible with one another, normally favouring the inactive state.
The binding of agonists makes the Equilibrium shift from R to R* to produce a biological effect.
Antagonists are drugs that bind to the receptor but do not enhance the fraction of R*, instead stabilizing the fraction of R.
Some medications like (Partial Agonists) shift the Equilibrium from R to R* but the fraction of R* is less than that produced by an Agonist.
The magnitude of Biological impact is directly related to the fraction of R*. In summary, Agonists, Antagonists, and Partial-Agonists are examples of Molecules or Ligands that bind to the activated site of the receptor and can affect the fraction of R*.
Types of receptors
Following are the types of receptors,
1. Transmembrane ligand-gated Receptors
2. G Protein-Coupled Receptor
3. Enzyme-linked Receptors
4. Intracellular Receptors
1. Transmembrane ligand-gated Receptors
Ligand-gated ion channels are integral membrane proteins that contain a pore that allows the flow of selected ions across the plasma membrane.
Ion flux is passive and driven by the electrochemical gradient e.g (GABA).
Explanation
The drug-binding site is present in the Extracellular region of ligand-gated ion channels. This site initiates the opening of the pore through which ions can flow across the Cell Membrane. The channel is typically closed until the Receptor is triggered by an Agonist, which opens the channel for a few milliseconds.
Depending on the ion conduction through these channels, these receptors intervene in different functions, including neurotransmission and muscle contraction.
Example
Stimulation of the nicotinic receptor by acetylcholine opens a channel that allows sodium inflow and potassium outflow across the cell membranes of neurons or Muscle cells. This change in ionic concentrations across the membrane produces an Action Potential in a Neuron and contraction in Skeletal and Cardiac Muscle.
2.G Protein-Coupled Receptor
G protein-coupled receptors (GPCRs), are integral Membrane Proteins, which are used to transform extracellular signals into Intracellular responses, such as Hormones and Neurotransmitters.
Examples
Inflammatory substances Prostaglandin, E2 receptors.
Explanation
The Extracellular Portion of this Receptor has the Ligand-Binding site, and the Intracellular Portion interacts with a G Protein in an activated form.
There are various kinds of G proteins (for example, Gs, Gi, and Gq), but all kinds are composed of three protein subunits (The α subunit, the β subunit, and the γ subunit). The α subunit binds with (GTP) Guanosine Triphosphate. β and γ subunits bind with G -Protein in the Cell Membrane.
The binding of an Agonist to the receptor increases GTP binding to the α subunit, causing the separation of the α-GTP complex from the βγ complex.
The α and βγ subunits are free to interact with particular Cellular Effectors, generally, an Enzyme or an ion channel, that cause further actions within the cell.
These responses generally last for several seconds to minutes. Often, the activation of effectors generates the “second messenger” molecules that further activate other effectors in the cell, causing a signal cascade effect.
3. Enzyme-linked receptor
An enzyme-linked receptor also called a Catalytic Receptor,is Transmembrane receptor,where the binding of an extracellular ligand results in enzymatic activity on the intracellular side. So the catalytic receptor is a vital membrane protein possessing both Catalytic, and Receptor functions. E.g. Receptor Tyrosine Kinase.
Explanation
Enzyme-Linked receptors activated by Ligand-Gated ions result in increased Enzyme activity, it has two important functions Intracellular Enzyme activity and Extracellular Enzyme Activity which has a Catalytic function.
The signalling molecule binds to the receptor on the outside of the cell and causes a conformational change in the catalytic function located on the receptor inside of the cell. So enzyme-linked receptors usually cause a signal cascade effect that is caused by G protein-coupled receptors.
Example
For example, the Enzymatic Activity includes Growth Factor Receptors and Tyrosine kinase Receptors.
4. Intracellular receptor
Intracellular receptors are those receptors that are not present on the cell membrane but rather are found inside the cell.
Thyroid and steroid hormones are examples of Hormones that interact with intracellular receptors.
The ligands that bind to them are often extracellular lipophilic hormones like steroid hormones and intracellular second messengers like inositol trisphosphate (IP3).
Examples
E.g transcription factors, and nuclear receptors.
Explanation
These receptors placed inside the cell rather than on its cell membrane include Thyroid and steroid hormones, it has sufficient lipid solubility & diffuse into the cell and interact with receptors.
The primary target of activated intracellular receptors is Transcription factors in the cell nucleus that initiates Gene Expression.
The activation or inactivation of transcription factors changes the transcription of DNA to RNA resulting in the translation of RNA into proteins.
In addition, structural proteins, Enzymes, RNA, and Ribosomes are targets of intracellular ligands.
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