TAARs

You have heard of the classic type of odor receptor in the nose, the type that senses the aromas of flowers and fruit and so much else. Did you know that there is a second type of odorant receptor?

These receptors are called “TAARs,” which stands for Trace Amine-Associated Receptors. They have also been called Trace Amine Receptors (TAs or TARs), though the former appellation may be more appropriate because we do not know as yet the full repertoire of molecules that bind to these receptors. 

Their existence was first described in 2001, their discovery the result of searching for genes coding for proteins with certain characteristics.* In the case of the TAARs the characteristic in question is the ability to bind to amine compounds such as dopamine and amphetamine. 

Humans have 6 functional genes for TAARs and 3 pseudogenes (= genes that have changed enough through human evolution that they no longer produce functional proteins). Of the functional gene products, one (TAAR1) exists in multiple tissues but not the olfactory tissue, and the rest (TAAR 2, 5, 6, 8s, and 9) appear to exist only in olfactory tissue. These receptors can be found on cells similar in both structure and location to regular olfactory cells, and they send their messages through the olfactory bulbs, just like regular olfactory neurons.**

What message do these TAARs send?  “STENCH!!!”

As anyone who has experienced Icelandic hákarl—fermented shark—can tell you, the process of letting fish rot creates a distinct and utterly foul smell. The chemical that imparts this stench: trimethylamine; the receptor that responds to it: TAAR5. (According to Wikipedia, Chef Anthony Bourdain described kæstan hákarl as "the single worst, most disgusting and terrible tasting thing" he has ever eaten—and he has eaten plenty of disgusting things!)

Hákarl hanging to dry in Bjarnahöfn in 2005. Photo by Chris 73 (Wikimedia Commons). 

Other compounds that bind to human TAARs: 

• phenethylamine, which lends its power to the stench of carnivore urine; this compound induces fear in rodents and serves as a warning to humans that, say, a tiger is nearby—when tigers mark their territory with urine, phenethylamine provides much of the urine’s persistent and aversive odor.
• tyramine, which occurs in certain cheeses, chocolate, and red wine, and—I might add—pu-erh; its odor has been characterized as meaty and dirty, but also as sweet and vegetal.***
• N-methylpiperidine, which, as its name implies, occurs in pepper—I believe that it gives that slightly sour unpleasant smell to old ground pepper, though I cannot be certain.

The total number of compounds to which TAARs respond is not known. One can say, however, that many of the known compounds contribute significantly to urinaceous and rotting smells.

Interestingly, some humans have genetic variants of the TAARs that lead to inability to sense some of these smells.**** Lucky them—or perhaps not—I guess it depends on the circumstances!

* Borowsky B, et al. (2001). Trace amines: identification of a family of mammalian G protein-coupled receptors. PNAS 98 (16): 8966–71. doi:10.1073/pnas.151105198; Bunzow JR, et al. (2001). Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol. Pharmacol. 60 (6): 1181–8. doi:10.1124/mol.60.6.1181. 

** Stephen D Liberles. Trace amine-associated receptors: ligands, neural circuits, and behaviors. Current Opinion in Neurobiology. Volume 34, October 2015, Pages 1–7.

*** “Our results showed that among 207 kinds of tea tested, Pu’er ripe tea contains the most kinds of and the highest content of the biogenic amines, followed by Pu’er sun dried tea, and Pu’er raw tea contains the least. The method should be helpful for the quantification of biogenic amines in the tea product and the tea quality control.” Mengying Zhang et al. Determination of Eight Different Biogenic Amines in Pu'er Tea by HPLC. Focusing on Modern Food Industry (FMFI) Volume 3, 2014 doi: 10.14355/fmfi.2014.03.009.

**** Vanti WB et al. Discovery of a null mutation in a human trace amine receptor gene. Genomics. 2003 Nov; 82(5):531-6.