<p>Each receptor has its own story of discovery. I'll share here the methods used by <a href="https://www.nobelprize.org/prizes/chemistry/2012/lefkowitz/facts/" rel="nofollow noreferrer">Lefkowitz</a> that led to the discovery of one of the first neurotransmitter receptors, namely the <a href="https://en.wikipedia.org/wiki/Adrenergic_receptor" rel="nofollow noreferrer">β2 adrenergic receptor</a> (β2AR) from frog erythrocytes in 1981. With this I mean β2AR was among the first receptors that was identified, purified, and characterized both at the protein and DNA level.</p>

<p>Lefkowitz's team was the first to uncover the charactistics of a neurotransmitter  at the protein and DNA level. βARs are involved in regulating cardiovascular function. Lefkowitz was awarded the <a href="https://www.nobelprize.org/prizes/chemistry/2012/lefkowitz/facts/" rel="nofollow noreferrer">Noble prize</a> for his early pioneering work on the discovery of these receptors. </p>

<p>His method was based on several steps, namely:</p>

<ul>
<li>The development of a novel and specific <a href="https://en.wikipedia.org/wiki/Ligand_binding_assay" rel="nofollow noreferrer">radioligand binding assay</a> to enable the measurement βAR-binding sites;</li>
<li>The identification of detergents to successfully solubilize a functional βAR from membrane preparations;</li>
<li>The synthesis of an affinity resin and photoaffinity ligands to facilitate receptor purification;</li>
<li>Reconstitution of the purified β2AR into phospholipid vesicles;</li>
<li>The demonstration that β2AR couples to, and activates the heterotrimeric G protein Gs and subsequent activation of adenylyl cyclase to produce cAMP;</li>
<li>Purified hamster β2AR was used for peptide sequencing that were subsequently used to synthesize oligonucleotides for cloning studies to isolate β2AR cDNA;</li>
</ul>

<p>After β1AR, Lefkowitz's lab soon purified β1AR, α1AR, and α2AR.</p>

<p><sub><strong>References</strong><br>
<strong>-</strong> <a href="https://www.sciencedirect.com/science/article/pii/S0092867412013621" rel="nofollow noreferrer">Benovic, <em>Cell</em> (2012); <strong>151</strong>(6): 1148-50</a><br>
<strong>-</strong> <a href="https://www.researchgate.net/publication/24261196_Historical_evolution_of_the_neurotransmission_concept" rel="nofollow noreferrer">Lopez-Munoz &amp; Alamo, <em>Neural Transm</em> (2009) <strong>116</strong>: 515–33</a></sub></p>

CC BY-SA 4.0
2020-05-15T15:14:39.313Z
It looks like nAChR was earlier by a couple years, compare https://neurotree.org/beta/publications.php?pid=8115 to references in https://www.mdpi.com/2218-273X/10/4/547 β2AR seems to be the first G-protein coupled receptor, though.
Bryan Krause
CC BY-SA 4.0
2020-05-14T19:28:08.200Z
2020-05-15T19:58:13.767Z
2020-05-15T19:58:13.767Z
AliceD
<p>Many neurotransmitter receptors are known, for example 5-HT<sub>2a</sub>, Mu, NMDA, and so on. How have these receptors been discovered?</p>

CC BY-SA 4.0
2020-05-14T15:04:20.853Z
Now? Or originally?
Bryan Krause
<neuroscience>
How are neurotransmitter receptors discovered?
julkarham
# How are neurotransmitter receptors discovered?

(Asked by: username_0 on 2020-05-14)

Many neurotransmitter receptors are known, for example 5-HT2a, Mu, NMDA, and so on. How have these receptors been discovered?

**Tags:** neuroscience

> **Comments:**
> **username_1**: Now? Or originally?  

---

## 1 answers

### Answer by username_2 on 2020-05-14. Score: 2

Each receptor has its own story of discovery. I'll share here the methods used by [Lefkowitz](https://www.nobelprize.org/prizes/chemistry/2012/lefkowitz/facts/) that led to the discovery of one of the first neurotransmitter receptors, namely the [β2 adrenergic receptor](https://en.wikipedia.org/wiki/Adrenergic_receptor) (β2AR) from frog erythrocytes in 1981. With this I mean β2AR was among the first receptors that was identified, purified, and characterized both at the protein and DNA level.

Lefkowitz's team was the first to uncover the charactistics of a neurotransmitter at the protein and DNA level. βARs are involved in regulating cardiovascular function. Lefkowitz was awarded the [Noble prize](https://www.nobelprize.org/prizes/chemistry/2012/lefkowitz/facts/) for his early pioneering work on the discovery of these receptors.

His method was based on several steps, namely:

* The development of a novel and specific [radioligand binding assay](https://en.wikipedia.org/wiki/Ligand_binding_assay) to enable the measurement βAR-binding sites;
* The identification of detergents to successfully solubilize a functional βAR from membrane preparations;
* The synthesis of an affinity resin and photoaffinity ligands to facilitate receptor purification;
* Reconstitution of the purified β2AR into phospholipid vesicles;
* The demonstration that β2AR couples to, and activates the heterotrimeric G protein Gs and subsequent activation of adenylyl cyclase to produce cAMP;
* Purified hamster β2AR was used for peptide sequencing that were subsequently used to synthesize oligonucleotides for cloning studies to isolate β2AR cDNA;

After β1AR, Lefkowitz's lab soon purified β1AR, α1AR, and α2AR.

**References**  
**-** [Benovic, *Cell* (2012); **151**(6): 1148-50](https://www.sciencedirect.com/science/article/pii/S0092867412013621)  
**-** [Lopez-Munoz & Alamo, *Neural Transm* (2009) **116**: 515–33](https://www.researchgate.net/publication/24261196_Historical_evolution_of_the_neurotransmission_concept)

> **Comments:**
> **username_1**: It looks like nAChR was earlier by a couple years, compare https://neurotree.org/beta/publications.php?pid=8115 to references in https://www.mdpi.com/2218-273X/10/4/547 β2AR seems to be the first G-protein coupled receptor, though.  

---

