Intracellular Receptors

In biochemistry and pharmacology, receptors are protein-based chemical structures that receive and transmit signals that can be integrated into biological systems. A ligand is an ion or molecule that binds to a central metal atom to form a coordination complex in coordination chemistry. Bonding with metals typically entails the formal donation of one or more of the ligand’s electron pairs, often via Lewis Bases Although there are many kinds of receptors, they can be categorized into two groups: 

• Cell surface receptors, which are found in the plasma membrane, and 
• Intracellular receptors are found inside the cell.

Intracellular Receptors

The receptors present within the cells, typically in the cytoplasm or nucleus, are proteins referred to as intracellular receptors. 

The ligands of intracellular receptors are often small, hydrophobic (hating) molecules because they must cross the plasma membrane to reach their receptors. For instance, intracellular membranes serve as the main receptors for hydrophobic steroid hormones, including the sex hormones estradiol (an estrogen) and testosterone.

When a hormone enters a cell and attaches to its receptor, the receptor is altered, allowing the complex of the receptor and hormone to enter the nucleus and control gene activity. Regions of the receptor that are capable of attaching to particular DNA sequences are made visible by hormone binding. These sequences are located near to specific genes in the cell’s DNA, and when the receptor binds there, it changes the transcription rate of those genes.

Types of Intracellular Receptors

Type I intracellular receptors

Chaperone proteins serve as anchors for type I intracellular receptors, sometimes referred to as cytoplasmic receptors, in the cytoplasm of a cell. Additionally, these proteins maintain the receptors’ dormant state.

The chaperone proteins separate from the type I intracellular receptor when a ligand attaches to it (creating the “ligand-receptor complex”. This allows the receptor to form a homodimer with other receptors and go through conformational change, exposing a nuclear localization sequence. The receptor can now access the cell’s nucleus thanks to this change. The ligand-receptor complex then triggers the start of transcription by binding to particular regulatory regions in chromosomal DNA through its DNA-binding region.

Progesterone and androgen receptors are two instances of type I intracellular receptors. Testosterone and dihydrotestosterone (DHT) are androgen receptor ligands that bind to androgen receptors in the cytoplasm and move them to the nucleus, starting cellular processes such as protein synthesis, cell proliferation, gonad formation, and the emergence of secondary sex characteristics. Contrarily, the menstrual cycle and other biological processes, such as transcription, are affected when the ligand progesterone binds to progesterone receptors in the cytoplasm.

Type II Intracellular receptors

The nucleus of a cell contains type II intracellular receptors, also referred to as nuclear receptors. Type II intracellular receptors can directly alter transcription without undergoing translocation because they are already in the nucleus. Usually, they combine with other nuclear receptors to create heterodimers. Retinoic acid receptors and thyroid receptors are two examples of type II intracellular receptors.

Heart and metabolism functions are regulated by thyroid hormone receptors. A person’s metabolism slows down when their thyroid receptors are not sufficiently stimulated, such as when they have hypothyroidism, and symptoms including weariness, lethargy, weight gain, and slowed heart rate result. When thyroid receptors are overstimulated (for instance, when a person has hyperthyroidism), their metabolism accelerates, which can cause a variety of symptoms such as anxiety, weight loss, and an accelerated heart rate.

Types of Signaling

The transmission of a signal from a sending cell to a receiving cell is referred to as cell-cell signaling. However, not all sending and receiving cells are adjacent, and not all cell pairs exchange signals in the same way. 

Chemical signaling in multicellular organisms is classified into four types: paracrine signaling, autocrine signaling, endocrine signaling, and direct contact signaling. The main distinction between signaling categories is the distance that the signal travels through the organism to reach the target cell.

Paracrine Signaling

Cells in proximity frequently communicate by releasing chemical messengers (ligands that can diffuse through the space between the cells). Paracrine signaling is a type of signaling in which cells communicate over relatively short distances. Paracrine signaling allows cells to coordinate their activities with their neighbors on a local level. Although paracrine signals are used in a variety of tissues and contexts, they are especially important during development because they allow one group of cells to tell another group of cells what cellular identity to adopt.

Synaptic Signaling

Synaptic signaling, in which nerve cells transmit signals, is an example of paracrine signaling. Synapse is the junction between two nerve cells where signal transmission occurs, and is named after this process. When a neuron fires, an electrical impulse travels quickly through the cell, down a long, fibre-like extension called an axon. 

Autocrine Signaling

Autocrine signaling occurs when a cell communicates with itself by releasing a ligand that binds to receptors on its own surface (or, depending on the type of signal, to receptors inside the cell). This may seem strange for a cell to do, but autocrine signaling is important in many processes. Autocrine signaling, for example, is critical during development, assisting cells in adopting and reinforcing their correct identities. Autocrine signaling is important in cancer treatment and is thought to play a role in metastasis. A signal may have both autocrine and paracrine effects in many cases, binding to the sending cell as well as other similar cells in the area.

Endocrine Signaling

When cells need to send messages over long distances, they frequently use the circulatory system as a distribution network. Signals are produced by specialized cells and released into the bloodstream, where they are carried to target cells in distant parts of the body. Hormones are signals that are produced in one part of the body and travel through the circulation to reach distant targets. 

Endocrine glands that release hormones in humans include the thyroid, hypothalamus, pituitary, gonads (testes and ovaries), and pancreas. Each endocrine gland produces one or more hormones, many of which act as master regulators of development and physiology.

Various Ligand Types

There are many distinct types of ligands, which are produced by signaling cells and interact with receptors in or on target cells. Others are hydrophobic molecules like steroids, while still others are gases like nitric oxide. Some are proteins.

Ligands that can enter the Cell

• The female sex hormone estradiol, which is a form of estrogen, and the male sex hormone testosterone are both common steroid hormones. 
• Another example of a steroid hormone is the substance known as vitamin D, which is created in the skin using light energy. 
• These hormones must connect to carrier proteins in order to pass through the (watery) bloodstream because they are hydrophobic and can easily permeate the plasma membrane.
• A ligand is a gas called nitric oxide (NO). Its small size allows it to permeate straight across the plasma membrane, similar to steroid hormones. 
• One of its primary functions is to trigger a signaling pathway that causes the smooth muscle around blood vessels to relax, allowing the blood vessels to enlarge (dilate). 
• In truth, nitroglycerin is a medication that treats heart illness by causing the production of NO, which dilates blood vessels and improves heart blood flow.
• NO has gained more recognition recently since Viagra and other erectile dysfunction prescription drugs target the pathway that NO impacts.

Ligands that bind on the outside of the Cell

• Because they are polar or charged, water-soluble ligands find it difficult to pass the plasma membrane.
• As a result, the majority of water-soluble ligands attach to the extracellular domains of cell-surface receptors and remain on the cell’s surface.
• The broadest class of water-soluble ligands is composed of peptide (protein) ligands. For instance, this group includes hormones like insulin, some neurotransmitters, and growth factors. 
• Peptide ligands can be as short as a few amino acids, as the pain-relieving enkephalins, or as long as a hundred amino acids or more.
• Neurotransmitters can also be proteins. However, many additional neurotransmitters are tiny chemical molecules called hydrophilic (water-loving) molecules. 
• Standard amino acids like glutamate and glycine are found in some neurotransmitters, whilst other modified or non-standard amino acids are found in others. 

FAQs on Intercellular Receptors

Question 1: What hormone is known to have intracellular receptors?

Answer:

Steroid hormones pass through a target cell’s plasma membrane and bind to intracellular receptors in the cytoplasm or nucleus. Steroid hormone-induced cell signaling pathways regulate specific genes in the cell’s DNA.

Question 2: Is cortisol a hormone with intracellular receptors?

Answer:

Both cortisol and aldosterone exert their effects after the uptake of free hormone from the circulation and binding to intracellular receptors known as the glucocorticoid receptor (GR, encoded by NR3C1) and the mineralocorticoid receptor (MR, encoded by NR3C1) (MR, encoded by NR3C2).

Question 3: When intracellular receptors are activated, what happens?

Answer:

When receptors are activated, they produce small molecules known as second messengers, which initiate and coordinate intracellular signaling pathways. Cyclic AMP (cAMP), for example, is a common second messenger involved in signal transduction cascades.

Question 4: What are some intracellular receptor examples?

Answer:

Thyroid hormones and a large group of steroid hormones, including glucocorticoids, mineralocorticoids, and sex steroid hormones, are examples.

Question 5: Where can you find intracellular receptors?

Answer:

Intracellular receptors are receptor proteins found within the cell, usually in the cytoplasm or nucleus. Most intracellular receptor ligands are small, hydrophobic (anti-water) molecules that must be able to cross the plasma membrane in order to reach their receptors.

Question 6: What do you mean by extracellular receptors?

Answer:

Extracellular signaling receptors are divided into two groups based on their location within the cell: cell surface receptors, which are found on the plasma membrane, and nuclear transcription factor receptors, which are found inside the cell.