ArtsAutosBooksBusinessEducationEntertainmentFamilyFashionFoodGamesGenderHealthHolidaysHomeHubPagesPersonal FinancePetsPoliticsReligionSportsTechnologyTravel

How drugs work? - Different drug receptors (eg Tyrosine Kinase receptors, Hormone receptors, nuclear receptors) - ePharm

Updated on October 2, 2017

Welcome to ePharmacology! Today we will discuss how a drug acts.

Nowadays it has been possible to understand the mechanism of action of many drugs.

Some drugs act by interacting with their specific receptors.

Some drugs produce their effects by modifying the ion channels.

There are a number of drugs that produce their response by interacting with enzymes or carrier proteins.

In addition, some drugs act simply by physical or chemical reaction.

Let's discuss about receptors!

Did you know?

Ligands are neurotransmitters, hormones, autocoides, and a large number of drugs. These substances are also called first messengers.

How drugs work?
How drugs work? | Source

What is a Receptor?

Receptor is the component of the cell to which a ligand (a molecule that binds to another molecule) specifically binds and may produce responses. For example, acetylcholine specifically binds with cho­linergic receptor but not with histamine receptor. Some drugs also bind with plasma proteins or erythrocytes. But these binding are nonspecific and are not related with the receptor.

The concept of receptor was originally coined independently by the experimental work of P Ehrlich (a German physician, biologist, chemist) and J. N. Langley (an English physiologist) in latter part of nineteenth and early part of twentieth centuries. Their experiments showed that nicotine, an alkaloid obtained from tobacco, caused contraction of skeletal muscle. South American arrow poison curare inhibited nicotine-induced contraction of skeletal muscle. But the response of that muscle to direct electrical stimulation was not blocked. The response to nicotine persisted even after denervation of the muscle. From this initial experiment. they concluded that nicotine and curare acted on the same component of the cell.

Subsequently, it had been possible to identify a number of receptors and their specific agonist and antagonists. Isolation of receptors with their subunits and determination of modular weight have greatly enriched this field.

Agonist vs Antagonist
Agonist vs Antagonist | Source

Receptors in 5 minutes

Where are receptors located?

Most of the receptors are located at the plasma membrane (what is the plasma membrane?). But receptors for steroid hormones, thyroid hormones, or vitamin D are located within the cell. At the synapse, receptors are located both on presynaptic and postsynaptic sites. Presynaptic receptors are called autoreceptors. The function of autoreceptors are to regulate the synthesis and release of neurotransmitters, α2-adrenergic receptors, M2 receptors, and H3 receptors are the examples of autoreceptors.

After identification of opioid receptors to which morphine and related drugs act, the investigators tried to find out the endogenous substances that usually acted on those receptors. Subsequently, in 1975, the existence of endogenous peptides such as met-enkephalin, leu-enkcphalin, dynorphin had been established that acted on opioid receptors.

The term orphan receptor has been applied for which no functional ligand is identified.

What happens if receptors don't function normally?

A number of diseases develop due to abnormality in receptors. For example, an autoimmune attack on nicotinic cholinergic receptor causes myesthenia gravis. Inherited mutation of ACTH receptor leads to the development of resistance to ACTH.

Overview of how receptors word
Overview of how receptors word | Source

What are the different types of Receptors? Classification of Receptors:

Receptors can be classified into four types on the basis of mechanism of action.

These are:

(Click to go to specific section)

  1. Ion-channel coupled receptors
  2. G protein-coupled receptors
  3. Tyrosine kinase related receptors
  4. DNA-linked receptors

The different types of receptors
The different types of receptors | Source

Ion channel linked receptor

Ion channel-coupled receptors

There are a number of receptors (e.g. nicotinic cholinergic receptor, GABAA receptor, glycine receptor, 5-HT3 receptor, and P2x receptor) which act by opening the ion channels. This type of receptors are present at the outer surface of the plasma membrane.

Ion channel coupled receptors
Ion channel coupled receptors | Source

Did you know?

α-Bungarotoxin is a peptide, having molecular weight of 7,800, obtained from the snake venom. It has high affinity for the nicotinic cholinergic receptor with slow rate of dissociation. Radio-labeled α-Bungarotoxin is used as a marker during solubilization and purification of the receptor.

Patients suffering from myasthenia gravis have impaired neuromuscular transmission primarily by noncompetitive mechanisms. In congenital myasthenia gravis, neuromuscular transmission can be impaired by mutations which alter the function of nicotinic cholinergic receptor.

Among these receptors, the molecular structure of nicotinic cholinergic receptor has been extensively studied. It is due to availability of source of receptors in high density and abundance (electric organs of the fish Torpedo and Electrophorus) and highly selective markers (e.g. α-bungarotoxin, cobra α-toxin) for the recep­tor.

The number of nicotinic cholinergic receptors in Torpedo electric organ is 1000 times more than that present in skeletal muscle. Nicotinic cholinergic re­ceptor in skeletal muscle is a pentamer of four distinct subunits: α2βγδ. It has a molecular weight of about 280 kDa. The subunits are arranged around a funnel shaped central cavity, with the largest portion of the receptor being exposed towards the extracellular space. The central cavity is believed to be the ion channel, to a diameter of about 6.5 Å. The open channel is selective for cations. But carboxy terminus (C) and long amino terminus (N) are located extracellularly. The amino termini of the two α-subunits are believed to contain the acetylcho­line-binding site.

G protein receptors

G protein-coupled receptors

Binding to this type of receptor leads to involvement of G proteins.

The G pro­tein-coupled receptors include:

Mechanism of action of G protein coupled receptors
Mechanism of action of G protein coupled receptors | Source
G protein coupled receptors
G protein coupled receptors

Among these receptors, β-adrenergic receptor has been first fully characterized. β-Adrenergic receptor possesses seven transmembrane α-helices with both the extracellular amino terminus and the intracellular carboxy terminus vary greatly in length. Another highly variable region is the long third cytoplasmic loop that couples to the G protein. Deletion or modification of this section causes the receptor to bind with the agonist but can not associate with G protein. The ligand-binding domain appears to be present within the membrane on one or more of the α-helical segments, but not on the extracellular amino-terminus.

Classes of G protein-coupled receptors (GPCR) and the G proteins they regulate.
Classes of G protein-coupled receptors (GPCR) and the G proteins they regulate. | Source

Tyrosine kinase receptors

Tyrosine kinase-linked membrane receptors

Tyrorine kinase-linked membrane receptors are:

  • Insulin receptors
  • Insulin­like growth factor 1 receptors
  • Epidermal growth factor receptors
  • Platelet-derived growth factor receptors

Tyrosine kinase linked receptor
Tyrosine kinase linked receptor | Source

These receptors produce their responses both rapidly (i.e. metabolic response within a few minutes) or and slowly (i.e. regulation of DNA synthesis after many hours).

Tyrorine kinase-linked receptors are present at the plasma membrane and have two functional domains: an extracellular ligand binding domain, which is enriched in cysteine residues, and a cytoplasmic domain, which possesses the tyrosine kinase activity as well as the sites of autophosphorylation.

The extracel­lular part of insulin or insulin like growth factor 1 receptor contains two dissimilar chains (α and β) while the epidermal growth factor contains a single polypeptide. The tyrosine kinase domain of these receptors is similar.

Intracellular DNA linked receptors

DNA-linked receptors

DNA-linked receptors are intracellular receptors and are soluble proteins. Retinoic acid, corticosteroids, thyroid hormone, and vitamin D act by binding with these type of receptors.

These receptors are composed of ligand binding domain and a DNA-binding domain in its middle part. The structure of the DNA-binding domain involves coordination of a zinc atom by four cysteine residues which together form a structure called a zinc finger.

The fingers are believed to wrap around the DNA helix. Agonist first enters the cell and binds with a cytoplasmic receptor, which is normally associated with two molecules of 90 kDa heat shock protein (HSP90). The agonist displaces HSP90 and the agonist-receptor complex then translocates to the nucleus. Within the nucleus, the agonist-receptor complex can recognize specific base sequences and activates specific genes.


DNA-linked receptors
DNA-linked receptors | Source

Receptors made simple

Was this article helpful?

See results

That's all for today!

In the next article we will discuss about individual receptors in more detail. So keep coming back to ePharmacology!

If you have any suggestions or if you want me to write about any topic then please feel free to send me a request!

Don't forget to comment on this article below!

© 2015 Oyon B

Comments

    0 of 8192 characters used
    Post Comment

    No comments yet.

    working

    This website uses cookies

    As a user in the EEA, your approval is needed on a few things. To provide a better website experience, hubpages.com uses cookies (and other similar technologies) and may collect, process, and share personal data. Please choose which areas of our service you consent to our doing so.

    For more information on managing or withdrawing consents and how we handle data, visit our Privacy Policy at: https://hubpages.com/privacy-policy#gdpr

    Show Details
    Necessary
    HubPages Device IDThis is used to identify particular browsers or devices when the access the service, and is used for security reasons.
    LoginThis is necessary to sign in to the HubPages Service.
    Google RecaptchaThis is used to prevent bots and spam. (Privacy Policy)
    AkismetThis is used to detect comment spam. (Privacy Policy)
    HubPages Google AnalyticsThis is used to provide data on traffic to our website, all personally identifyable data is anonymized. (Privacy Policy)
    HubPages Traffic PixelThis is used to collect data on traffic to articles and other pages on our site. Unless you are signed in to a HubPages account, all personally identifiable information is anonymized.
    Amazon Web ServicesThis is a cloud services platform that we used to host our service. (Privacy Policy)
    CloudflareThis is a cloud CDN service that we use to efficiently deliver files required for our service to operate such as javascript, cascading style sheets, images, and videos. (Privacy Policy)
    Google Hosted LibrariesJavascript software libraries such as jQuery are loaded at endpoints on the googleapis.com or gstatic.com domains, for performance and efficiency reasons. (Privacy Policy)
    Features
    Google Custom SearchThis is feature allows you to search the site. (Privacy Policy)
    Google MapsSome articles have Google Maps embedded in them. (Privacy Policy)
    Google ChartsThis is used to display charts and graphs on articles and the author center. (Privacy Policy)
    Google AdSense Host APIThis service allows you to sign up for or associate a Google AdSense account with HubPages, so that you can earn money from ads on your articles. No data is shared unless you engage with this feature. (Privacy Policy)
    Google YouTubeSome articles have YouTube videos embedded in them. (Privacy Policy)
    VimeoSome articles have Vimeo videos embedded in them. (Privacy Policy)
    PaypalThis is used for a registered author who enrolls in the HubPages Earnings program and requests to be paid via PayPal. No data is shared with Paypal unless you engage with this feature. (Privacy Policy)
    Facebook LoginYou can use this to streamline signing up for, or signing in to your Hubpages account. No data is shared with Facebook unless you engage with this feature. (Privacy Policy)
    MavenThis supports the Maven widget and search functionality. (Privacy Policy)
    Marketing
    Google AdSenseThis is an ad network. (Privacy Policy)
    Google DoubleClickGoogle provides ad serving technology and runs an ad network. (Privacy Policy)
    Index ExchangeThis is an ad network. (Privacy Policy)
    SovrnThis is an ad network. (Privacy Policy)
    Facebook AdsThis is an ad network. (Privacy Policy)
    Amazon Unified Ad MarketplaceThis is an ad network. (Privacy Policy)
    AppNexusThis is an ad network. (Privacy Policy)
    OpenxThis is an ad network. (Privacy Policy)
    Rubicon ProjectThis is an ad network. (Privacy Policy)
    TripleLiftThis is an ad network. (Privacy Policy)
    Say MediaWe partner with Say Media to deliver ad campaigns on our sites. (Privacy Policy)
    Remarketing PixelsWe may use remarketing pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to advertise the HubPages Service to people that have visited our sites.
    Conversion Tracking PixelsWe may use conversion tracking pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to identify when an advertisement has successfully resulted in the desired action, such as signing up for the HubPages Service or publishing an article on the HubPages Service.
    Statistics
    Author Google AnalyticsThis is used to provide traffic data and reports to the authors of articles on the HubPages Service. (Privacy Policy)
    ComscoreComScore is a media measurement and analytics company providing marketing data and analytics to enterprises, media and advertising agencies, and publishers. Non-consent will result in ComScore only processing obfuscated personal data. (Privacy Policy)
    Amazon Tracking PixelSome articles display amazon products as part of the Amazon Affiliate program, this pixel provides traffic statistics for those products (Privacy Policy)