View source for Receptor (biochemistry)

{{Short description|Protein molecule receiving signals for a cell}}
{{Other uses|Receptor (disambiguation)}}
[[File:Receptor (Biochemistry).svg|thumb|An example of membrane '''receptors'''. {{ordered list | Ligands, located outside the cell 
| Ligands connect to specific receptor proteins based on the shape of the active site of the protein. 
| The receptor releases a messenger once the ligand has connected to the receptor.}}
]]

In [[biochemistry]] and [[pharmacology]], '''receptors''' are chemical structures, composed of [[protein]], that receive and [[Signal_transduction|transduce]] signals that may be integrated into biological systems.<ref name="hall">{{cite book |last1=Guyton |first1=Arthur C. |last2=Hall |first2=John E. |url=https://books.google.com/books?id=3sWNCgAAQBAJ |year=2016 |title=Guyton and Hall Textbook of Medical Physiology |location=Philadelphia, PA |publisher= Elsevier Saunders |pages=930–937 |oclc=1027900365 |isbn=9781455770052}}</ref> These signals are typically chemical messengers{{refn|group=nb|In the case of the receptor [[rhodopsin]], the input is a [[photon]], not a chemical}} which bind to a receptor and produce [[physiological response]]s such as change in the [[electrophysiology|electrical activity of a cell]]. For example, [[GABA]], an inhibitory [[neurotransmitter]], inhibits electrical activity of neurons by binding to [[GABAA receptor|GABA{{sub|A}} receptor]]s.<ref>{{Cite journal |last1=Mihic |first1=S. John |last2=Harris |first2=R. Adron |date=1997 |title=GABA and the GABA{{sub|A}} Receptor |journal=Alcohol Health and Research World |volume=21 |issue=2 |pages=127–131 |issn=0090-838X |pmc=6826832 |pmid=15704348}}</ref> There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration.<ref name="alberts">{{cite book|last1=Alberts|first1=Bruce|last2=Bray| first2= Dennis|last3=Hopkin|first3=Karen|last4=Johnson|first4=Alexander|last5=Lewis|first5=Julian|last6=Raff|first6=Martin|last7=Roberts|first7=Keith|last8=Walter|first8=Peter | name-list-style = vanc |title=Essential Cell Biology| date= 2014|publisher= Science|location=New York, NY, USA|isbn=978-0-8153-4454-4|page=534|edition=Fourth}}</ref> Relaying sends the signal onward, amplification increases the effect of a single [[ligand (biochemistry)|ligand]], and integration allows the signal to be incorporated into another biochemical pathway.<ref name="alberts"/>

Receptor proteins can be classified by their location. [[Cell surface receptors]], also known as transmembrane receptors, include [[ligand-gated ion channel]]s, [[G protein-coupled receptor]]s, and enzyme-linked [[hormone receptor]]s.<ref name="hall"/> [[Intracellular receptor|Intracellular receptors]] are those found inside the cell, and include cytoplasmic receptors and [[nuclear receptor]]s.<ref name="hall"/> A molecule that binds to a receptor is called a [[ligand (biochemistry)|ligand]] and can be a protein, [[peptide]] (short protein), or another [[small molecule]], such as a [[neurotransmitter]], [[hormone]], pharmaceutical drug, toxin, [[Calcium-sensing receptor|calcium ion]] or parts of the outside of a virus or microbe. An endogenously produced substance that binds to a particular receptor is referred to as its endogenous ligand. E.g. the endogenous ligand for the [[nicotinic acetylcholine receptor]] is [[acetylcholine]], but it can also be activated by [[nicotine]]<ref>{{cite journal |last1=Gotti |first1=Cecilia |last2=Marks |first2=Michael. J. |last3= Millar |first3=Neil S. |last4=Wonnacott |first4=Susan |title=Nicotinic acetylcholine receptors (version 2019.4) |journal= IUPHAR/BPS Guide to Pharmacology CITE |date=16 September 2019 |volume=2019 |issue=4 |doi= 10.2218/gtopdb/F76/2019.4 |url=https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=76 |access-date=17 November 2020| doi-access=free }}</ref><ref name=MalenkaNicotine>{{cite book|vauthors=Malenka RC, Nestler EJ, Hyman SE|veditors=Sydor A, Brown RY|title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience|year=2009|publisher= McGraw-Hill Medical|location=New York|isbn=9780071481274|page=234|edition=2nd|chapter=Chapter 9: Autonomic Nervous System|quote=Nicotine&nbsp;... is a natural alkaloid of the tobacco plant. Lobeline is a natural alkaloid of Indian tobacco. Both drugs are agonists [of] nicotinic cholinergic receptors&nbsp;...}}</ref> and blocked by [[curare]].<ref>{{cite web |title=Curare Drug Information, Professional |url=https://www.drugs.com/mmx/curare.html |website=Drugs.com |access-date=8 December 2020 |language=en |archive-date=16 November 2018 |archive-url=https://web.archive.org/web/20181116073247/https://www.drugs.com/mmx/curare.html |url-status=dead }}</ref> Receptors of a particular type are linked to specific cellular biochemical pathways that correspond to the signal. While numerous receptors are found in most cells, each receptor will only bind with ligands of a particular structure. This has been analogously compared to [[Enzyme#.22Lock_and_key.22_model|how locks will only accept specifically shaped keys]]. When a ligand binds to a corresponding receptor, it activates or inhibits the receptor's associated biochemical pathway, which may also be highly specialised.

Receptor proteins can be also classified by the property of the ligands. Such classifications include [[Chemoreceptor|chemoreceptors]], [[Mechanoreceptor|mechanoreceptors]], [[gravitropism|gravitropic receptors]], [[Photoreceptor protein|photoreceptors]], [[Magnetoreception|magnetoreceptors]] and gasoreceptors.

== Structure ==
[[File:Transmembrane receptor.svg|thumb|right|Transmembrane receptor: E=extracellular space; I=intracellular space; P=plasma membrane]]
The structures of receptors are very diverse and include the following major categories, among others: 
* Type 1: [[Ligand-gated ion channel]]s (ionotropic receptors) – These receptors are typically the targets of fast neurotransmitters such as [[acetylcholine]] (nicotinic) and [[GABA]]; activation of these receptors results in changes in ion movement across a membrane. They have a heteromeric structure in that each subunit consists of the extracellular ligand-binding domain and a transmembrane domain which includes four transmembrane [[alpha helix|alpha helices]]. The ligand-binding cavities are located at the interface between the subunits.
* Type 2: [[G protein-coupled receptor]]s (metabotropic receptors) – This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e.g. dopamine, metabotropic glutamate. They are composed of seven transmembrane alpha helices. The loops connecting the alpha helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop.<ref name="pmid19912230">{{cite journal | vauthors = Congreve M, Marshall F | title = The impact of GPCR structures on pharmacology and structure-based drug design | journal = British Journal of Pharmacology | volume = 159 | issue = 5 | pages = 986–96 | date = March 2010 | pmid = 19912230 | pmc = 2839258 | doi = 10.1111/j.1476-5381.2009.00476.x }}</ref> The aforementioned receptors are coupled to different intracellular effector systems via [[G protein]]s.<ref name=" pmid=21873996 ">{{cite journal | vauthors = Qin K, Dong C, Wu G, Lambert NA | title = Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers | journal = Nature Chemical Biology | volume = 7 | issue = 10 | pages = 740–7 | date = August 2011 | pmid = 21873996 | pmc = 3177959 | doi = 10.1038/nchembio.642 }}</ref> G proteins are heterotrimers made up of 3 subunits: α (alpha), β (beta), and γ (gamma). In the inactive state, the three subunits associate together and the α-subunit binds GDP.<ref>{{Cite book| last=Zubay|first=Geoffrey|title=Biochemistry 4th Ed.|publisher=William C Brown Pub|year=1998|isbn=0697219003|location=Dubuque, IA|pages=684}}</ref> G protein activation causes a conformational change, which leads to the exchange of GDP for GTP. GTP-binding to the α-subunit causes dissociation of the β- and γ-subunits.<ref>{{Cite book|last1=Garrett|first1=Reginald|title=Biochemistry|last2=Grisham|first2=Charles|publisher=Cengage Learning|year=2012|isbn= 9781473733602|pages=1130}}</ref> Furthermore, the three subunits, α, β, and γ have additional four main classes based on their primary sequence. These include G<sub>s</sub>, G<sub>i</sub>, G<sub>q</sub> and G<sub>12</sub>.<ref>{{Cite journal| last1=Hamm|first1=Heidi E.|last2=Oldham|first2=William M.|date=2008|title=Heterotrimeric G Protein Activation by G-Protein-Coupled Receptors|url=|journal=Nature Reviews Molecular Cell Biology|publisher=Nature Publishing Group|volume=9|issue=1|pages=60–71|doi=10.1038/nrm2299|pmid=18043707|s2cid=24267759}}</ref>
* Type 3: Kinase-linked and related receptors (see "[[Receptor tyrosine kinase]]" and "[[Enzyme-linked receptor]]") – They are composed of an extracellular domain containing the ligand binding site and an intracellular domain, often with enzymatic-function, linked by a single transmembrane alpha helix. The [[insulin receptor]] is an example. 
* Type 4: [[Nuclear receptor]]s – While they are called nuclear receptors, they are actually located in the [[cytoplasm]] and migrate to the [[cell nucleus|nucleus]] after binding with their ligands. They are composed of a [[C-terminus|C-terminal]] ligand-binding region, a core [[DNA-binding domain]] (DBD) and an [[N-terminus|N-terminal]] domain that contains the ''AF1''(activation function 1) region. The core region has two zinc fingers that are responsible for recognizing the DNA sequences specific to this receptor. The N terminus interacts with other cellular transcription factors in a ligand-independent manner; and, depending on these interactions, it can modify the binding/activity of the receptor. Steroid and thyroid-hormone receptors are examples of such receptors.<ref name="Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G 2012">{{cite book |vauthors=Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G | year=2012 | edition= 7th | title= Rang & Dale's Pharmacology |publisher= Elsevier Churchill Livingstone |isbn= 978-0-7020-3471-8}}</ref>

Membrane receptors may be isolated from cell membranes by complex extraction procedures using [[Liquid-liquid extraction|solvents]], [[detergents]], and/or [[affinity purification]].

The structures and actions of receptors may be studied by using biophysical methods such as [[X-ray crystallography#Biological macromolecular crystallography|X-ray crystallography]], [[Nuclear magnetic resonance spectroscopy of proteins|NMR]], [[circular dichroism]], and [[dual polarisation interferometry]]. [[Computer simulation]]s of the dynamic behavior of receptors have been used to gain understanding of their mechanisms of action.

== Binding and activation ==
Ligand binding is an [[chemical equilibrium|equilibrium]] process. Ligands bind to receptors and dissociate from them according to the [[law of mass action]] in the following equation, for a ligand L and receptor, R. The brackets around chemical species denote their concentrations.

:<math chem>
{[\ce{L}] + [\ce{R}] \ce{<=>[{K_d}]} [\text{LR}]}
</math>

One measure of how well a molecule fits a receptor is its binding affinity, which is inversely related to the [[dissociation constant]] ''K''<sub>''d''</sub>. A good fit corresponds with high affinity and low ''K''<sub>''d''</sub>. The final biological response (e.g. [[second messenger system|second messenger cascade]], muscle-contraction), is only achieved after a significant number of receptors are activated.

Affinity is a measure of the tendency of a ligand to bind to its receptor. Efficacy is the measure of the bound ligand to activate its receptor.

=== Agonists versus antagonists ===
[[File:Efficacy spectrum.png|right|thumb|320px|Efficacy spectrum of receptor ligands.]]
Not every ligand that binds to a receptor also activates that receptor. The following classes of ligands exist:

* ''(Full) [[agonist]]s'' are able to activate the receptor and result in a strong biological response. The natural [[endogenous]] ligand with the greatest [[intrinsic activity|efficacy]] for a given receptor is by definition a full agonist (100% efficacy).
* ''[[Partial agonist]]s'' do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared to those of full agonists (efficacy between 0 and 100%).
* [[Receptor antagonist|''Antagonists'']] bind to receptors but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. Receptor antagonists can be competitive (or reversible), and compete with the agonist for the receptor,  or they can be irreversible antagonists that form [[covalent bonds]] (or extremely high affinity non-covalent bonds) with the receptor and completely block it. The proton pump inhibitor [[omeprazole]] is an example of an irreversible antagonist. The effects of irreversible antagonism can only be reversed by synthesis of new receptors. 
* ''[[Inverse agonist]]s'' reduce the activity of receptors by inhibiting their constitutive activity (negative efficacy).
* ''[[Allosteric regulation|Allosteric modulators]]'': They do not bind to the agonist-binding site of the receptor but instead on specific allosteric binding sites, through which they modify the effect of the agonist. For example, [[benzodiazepines]] (BZDs) bind to the BZD site on the [[GABAA receptor|GABA<sub>A</sub> receptor]] and potentiate the effect of endogenous GABA.

Note that the idea of receptor agonism and antagonism only refers to the interaction between receptors and ligands and not to their biological effects.

=== Constitutive activity ===
A receptor which is capable of producing a biological response in the absence of a bound ligand is said to display "constitutive activity".<ref name="Milligan_2003">{{cite journal | vauthors = Milligan G | title = Constitutive activity and inverse agonists of G protein-coupled receptors: a current perspective | journal = Molecular Pharmacology | volume = 64 | issue = 6 | pages = 1271–6 | date = December 2003 | pmid = 14645655 | doi = 10.1124/mol.64.6.1271 | s2cid = 2454589 }}</ref> The constitutive activity of a receptor may be blocked by an [[inverse agonist]]. The anti-obesity drugs [[rimonabant]] and [[taranabant]] are inverse agonists at the cannabinoid [[CB1 receptor]] and though they produced significant weight loss, both were withdrawn owing to a high incidence of depression and anxiety, which are believed to relate to the inhibition of the constitutive activity of the cannabinoid receptor.

The [[GABAA receptor|GABA<sub>A</sub> receptor]] has constitutive activity and conducts some basal current in the absence of an agonist. This allows [[beta carboline]] to act as an inverse agonist and reduce the current ''below'' basal levels.

Mutations in receptors that result in increased constitutive activity underlie some inherited diseases, such as [[precocious puberty]] (due to mutations in luteinizing hormone receptors) and [[hyperthyroidism]] (due to mutations in thyroid-stimulating hormone receptors).

== Theories of drug-receptor interaction ==

=== Occupation ===

Early forms of the [[receptor theory]] of pharmacology stated that a drug's effect is directly proportional to the number of receptors that are occupied.<ref>{{cite journal |last1=Rang |first1=HP |title=The receptor concept: pharmacology's big idea |journal=British Journal of Pharmacology |date=January 2006 |volume=147 |issue=Suppl 1 |pages=S9-16 |doi=10.1038/sj.bjp.0706457 |pmid=16402126 |pmc=1760743}}</ref> Furthermore, a drug effect ceases as a drug-receptor complex dissociates.

[[Everhardus Jacobus Ariëns|Ariëns]] & Stephenson introduced the terms  "affinity" & "efficacy" to describe the action of ligands bound to receptors.<ref name="pmid13229418">{{cite journal | vauthors = Ariens EJ | title = Affinity and intrinsic activity in the theory of competitive inhibition. I. Problems and theory | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 99 | issue = 1 | pages = 32–49 | date = September 1954 | pmid = 13229418 }}</ref><ref name="pmid13383117">{{cite journal | vauthors = Stephenson RP | title = A modification of receptor theory | journal = British Journal of Pharmacology and Chemotherapy | volume = 11 | issue = 4 | pages = 379–93 | date = December 1956 | pmid = 13383117 | pmc = 1510558 | doi = 10.1111/j.1476-5381.1956.tb00006.x }}</ref>

* [[Dissociation constant#Protein-ligand binding|Affinity]]: The ability of a drug to combine with a receptor to create a drug-receptor complex.
* [[Intrinsic activity|Efficacy]]: The ability of drug to initiate a response after the formation of drug-receptor complex.

=== Rate ===

In contrast to the accepted ''Occupation Theory'', Rate Theory proposes that the activation of receptors is directly proportional to the total number of encounters of a drug with its receptors per unit time. Pharmacological activity is directly proportional to the rates of dissociation and association, '''not''' the number of receptors occupied:<ref name="isbn0-12-643732-7">{{cite book | author = Silverman RB | title = The Organic Chemistry of Drug Design and Drug Action | edition = 2nd | publisher = Elsevier Academic Press | location = Amsterdam | year = 2004 | isbn = 0-12-643732-7 | chapter = 3.2.C Theories for Drug—Receptor Interactions | chapter-url = https://archive.org/details/organicchemistry00silv_0 | url-access = registration | url = https://archive.org/details/organicchemistry00silv_0 }}</ref>

* Agonist: A drug with a fast association and a fast dissociation.
* Partial-agonist: A drug with an intermediate association and an intermediate dissociation.
* Antagonist: A drug with a fast association & slow dissociation

=== Induced-fit ===

As a drug approaches a receptor, the receptor alters the conformation of its binding site to produce drug—receptor complex.

=== Spare Receptors ===

In some receptor systems (e.g. acetylcholine at the neuromuscular junction in smooth muscle), agonists are able to elicit maximal response at very low levels of receptor occupancy (<1%). Thus, that system has spare receptors or a receptor reserve. This arrangement produces an economy of neurotransmitter production and release.<ref name="Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G 2012"/>

== Receptor regulation ==
Cells can increase ([[upregulate]]) or decrease ([[downregulate]]) the number of receptors to a given [[hormone]] or [[neurotransmitter]] to alter their sensitivity to different molecules. This is a locally acting [[feedback]] mechanism.

* Change in the receptor conformation such that binding of the agonist does not activate the receptor. This is seen with ion channel receptors.
* [[Protein quaternary structure|Uncoupling]] of the receptor [[G protein-coupled receptor#G-protein activation/deactivation cycle|effector molecules]] is seen with G protein-coupled receptors.
* Receptor [[Endocytosis|sequestration]] (internalization),<ref>{{cite journal |vauthors=Boulay G, Chrétien L, Richard DE, Guillemette G |date= November 1994 |title= Short-term desensitization of the angiotensin II receptor of bovinde adrenal glomerulosa cells corresponds to a shift from a high to low affinity state |journal= Endocrinology |volume=135 |issue=5 |pages= 2130–6|doi=10.1210/en.135.5.2130|pmid= 7956936 }}</ref> e.g. in the case of hormone receptors.

== Examples and ligands ==

The ligands for receptors are as diverse as their receptors. GPCRs (7TMs) are a particularly vast family, with at least 810 members. There are also [[LGIC]]s for at least a dozen endogenous ligands, and many more receptors possible through different subunit compositions. Some common examples of ligands and receptors include:<ref name="boron">{{cite book | vauthors = Boulpaep EL, Boron WF |year=2005 |title= Medical Physiology: A Cellular and Molecular Approach |location= St. Louis, Mo |publisher= Elsevier Saunders |page=90 |isbn=1-4160-2328-3}}</ref>

=== Ion channels and G protein coupled receptors ===
{{Main|Ligand-gated ion channel|G protein-coupled receptor}}

Some example ionotropic (LGIC) and metabotropic (specifically, GPCRs) receptors are shown in the table below. The chief neurotransmitters are glutamate and GABA; other neurotransmitters are [[Neuromodulation|neuromodulatory]]. This list is by no means exhaustive.

{| class="wikitable"
|-
! rowspan="2"|Endogenous Ligand
!colspan="3"|[[LGIC|Ion channel receptor (LGIC)]]
!colspan="3"|[[7TM|G protein coupled receptor (GPCR)]]
|-
!Receptors
![[Electric_current|Ion current]]{{refn|group=nb|Different LGICs conduct currents of different [[ions]]. This is accomplished with selectivity filters, such as the [[Potassium_channel#Selectivity_filter|selectivity filter of the K+ ion channel]]}}
!Exogenous Ligand
!Receptors
![[G protein]]
!Exogenous Ligand
|-
|[[Glutamate]]
|[[iGluR]]s: [[NMDA receptor|NMDA]],<br> [[AMPA receptor|AMPA]], and [[Kainate receptors]]
|Na<sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup> <ref name="boron" />
|[[Ketamine]]
|[[Glutamate receptor]]s: [[mGluR]]s
|Gq or Gi/o
| -
|-
|[[GABA]]
|[[GABAA|GABA<sub>A</sub>]]<br>(including [[GABAA-rho|GABA<sub>A</sub>-rho]])
|Cl<sup>&minus;</sup> > HCO<sup>&minus;</sup><sub>3</sub> <ref name="boron" />
|[[Benzodiazepines]]
|[[GABAB|GABA<sub>B</sub> receptor]]
|Gi/o
|[[Baclofen]]
|-
|[[Acetylcholine]]
|[[Nicotinic acetylcholine receptor|nAChR]]
|Na<sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup><ref name="boron" />
|[[Nicotine]]
|[[Muscarinic acetylcholine receptor|mAChR]]
|[[Gq subunit|Gq]] or Gi
|[[Muscarine]]
|-
|[[Glycine]]
|[[Glycine receptor]] (GlyR)
|Cl<sup>&minus;</sup> > HCO<sup>&minus;</sup><sub>3</sub> <ref name="boron" />
|[[Strychnine]]
| -
| -
| -
|-
|[[Serotonin]]
|[[Serotonin receptor|5-HT<sub>3</sub> receptor]]
|Na<sup>+</sup>, K<sup>+</sup> <ref name="boron" />
|[[Cereulide]]
|[[Serotonin receptor|5-HT1-2 or 4-7]]
|Gs, Gi/o or Gq
|  -
|-
|[[Adenosine triphosphate|ATP]]
|[[P2X receptors]]
|Ca<sup>2+</sup>, Na<sup>+</sup>, Mg<sup>2+</sup>  <ref name="boron" />
|BzATP{{citation needed|date=April 2019}}
|[[P2Y receptors]]
|Gs, Gi/o or Gq
| -
|-
|[[Dopamine]]
|No ion channels{{Citation needed|date=April 2019}}
| -
| -
|[[Dopamine receptor]]
| Gs or Gi/o
| -
|-
|}

=== Enzyme linked receptors===
{{Main|Enzyme-linked receptor}}

Enzyme linked receptors include [[Receptor tyrosine kinase]]s (RTKs), serine/threonine-specific protein kinase, as in bone morphogenetic protein and guanylate cyclase, as in atrial natriuretic factor receptor. Of the RTKs, 20 classes have been identified, with 58 different RTKs as members. Some examples are shown below:

{| class="wikitable"
|-
!'''RTK Class/Receptor Family'''||'''Member'''||'''Endogenous Ligand'''
!'''Exogenous Ligand'''
|-
| I ||[[Epidermal growth factor receptor|EGFR]]||[[Epidermal growth factor|EGF]]
|[[Gefitinib]]
|-
| II ||[[Insulin receptor|Insulin Receptor]]||[[Insulin]]
|[[Chaetochromin]]
|-
| IV ||[[VEGF receptor|VEGFR]]||[[Vascular endothelial growth factor|VEGF]]
|[[Lenvatinib]]
|}

=== Intracellular Receptors ===
{{Main|Intracellular receptor}}

Receptors may be classed based on their mechanism or on their position in the cell. 4 examples of intracellular LGIC are shown below:

{| class="wikitable"
|-
! Receptor || Ligand || Ion current
|-
| [[cyclic nucleotide-gated ion channel]]s || [[cyclic guanosine monophosphate|cGMP]] ([[Visual system|vision]]), [[Cyclic adenosine monophosphate|cAMP]] and [[cyclic guanosine triphosphate|cGTP]] ([[Olfaction#Main olfactory system|olfaction]]) || Na<sup>+</sup>, K<sup>+</sup> <ref name=boron/> 
|-
| [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] || [[inositol triphosphate|IP<sub>3</sub>]] || Ca<sup>2+</sup> <ref name=boron/>
|-
| Intracellular [[Adenosine triphosphate|ATP]] receptors || [[Adenosine triphosphate|ATP]] (closes channel)<ref name=boron/> || K<sup>+</sup> <ref name=boron/>  
|-
| [[Ryanodine receptor]] || Ca<sup>2+</sup> || Ca<sup>2+</sup> <ref name=boron/>
|}

== Role in health and disease==
=== In genetic disorders ===
Many [[genetic disorder]]s involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the [[hormone]] is produced at decreased level; this gives rise to the "pseudo-hypo-" group of [[endocrinology|endocrine disorders]], where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.

=== In the immune system ===
{{Main article|Immune receptor}}
The main receptors in the [[immune system]] are [[pattern recognition receptors]] (PRRs), [[toll-like receptor]]s (TLRs), [[killer activated receptor|killer activated]] and [[killer inhibitor receptor]]s (KARs and KIRs), [[complement receptor]]s, [[Fc receptors]], [[B cell receptor]]s and [[T cell receptor]]s.<ref name="isbn0-7817-9543-5">{{cite book |vauthors=Waltenbaugh C, Doan T, Melvold R, Viselli S | title = Immunology |url=https://archive.org/details/lippincottsillus00doan |url-access=limited | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2008 | page = [https://archive.org/details/lippincottsillus00doan/page/n354 20] | isbn = 978-0-7817-9543-2 }}</ref>

== See also ==
* [[Ki Database|K<sub>i</sub> Database]]
* [[Ion channel linked receptors]]
* [[Neuropsychopharmacology]]
* [[Schild regression]] for ligand receptor inhibition
* [[Signal transduction]]
* [[Stem cell marker]]
* [[List of MeSH codes (D12.776)]]
* [[Receptor theory]]

==Notes==
{{reflist|group=nb}}

== References ==
{{Reflist|colwidth=35em}}

== External links ==
*[http://www.iuphar-db.org IUPHAR GPCR Database and Ion Channels Compendium] {{Webarchive|url=https://web.archive.org/web/20190323064157/http://iuphar-db.org/ |date=2019-03-23 }}
*[http://www.receptome.org/ Human plasma membrane receptome] {{Webarchive|url=https://web.archive.org/web/20190915010207/http://www.receptome.org/ |date=2019-09-15 }}
*{{MeshName|Cell+surface+receptors}}

{{Cell_signaling}}
{{Cell surface receptors}}
{{Immune receptors}}
{{Transcription factors|g2}}
{{genarch}}

[[Category:Receptors| ]]
[[Category:Cell biology]]
[[Category:Cell signaling]]
[[Category:Membrane biology]]