SIGMA RECEPTORS UNDER THE SEA
Like Sandy Cheeks, from the Classical Show SpongeBob SquarePants, who comes to live in Bikini Bottom from her hometown in Houston, Texas, the sigma receptor is predicted to exhibit this behavior when interacting with cell membrane receptors.
What is Translocation?
(Sambo et. al 2018) (S1 ep18)
This drug causes EAAT3 internalization in dopamine neurons
What is amphetamine?
the only two elements of the periodic table that are liquid at room temperature
What are mercury and bromine?
While recent news on ketamine is focused on its therapeutic potential for treatment resistant depression, this was its original use in medicine
What is anesthetic? (will also accept pain management)
TAAR1 is an acronym for this.
What is the trace amine associated receptor 1?
The trimeric structure of a sigma receptor has this many transmembrane domains, which also happens to coincide with the number of snail pets SpongeBob has owned.
What is 3?
Each protomer has a singular transmembrane structure (Schmidt et. al 2016) and SpongeBob has owned 3 snail pets: Gary, Larry and Jerry (S2 ep29)
Two disorders implicated in EAAT dysregulation
What are PTSD, depression, schizophrenia, bipolar disorder?
The number of hearts an octopus has
What is 3?
Two branchial hearts that pump blood through each of the gills, and the third heart is a systemic heart that pumps blood through the whole body.
At doses higher than those used for clinical applications, ketamine users will experience these symptoms.
What is hallucination and dissociation?
TAAR1 is this type of receptor. Hint: not ionotropic.
What is a G-protein coupled receptor (GPCR)?
Just as Patrick Star becomes inactive/sleepy as soon as Squidward starts playing his clarinet, the Sigma Receptor is thought to be dormant when it is complexed with this protein in the endoplasmic reticulum.
What is the Binding Immunoglobulin Protein or BiP?
(Hayashi & Su, 2007) (S1 ep4)
This function of EAATs is stoichiometrically uncoupled from glutamate transport
What is anion transport?
Sounds travels fastest through this phase of matter
What is solid?
This enantiomer (S or R) is the more active of the two and is used the one being used clinically for depression treatment.
What is S? (Name of drug is Esketamine, a play on this)
This is a TAAR1 agonist
What is amphetamine?
(Methamphetamine, tyramine, tryptamine, B-PEA, octopamine, 3-MT…..many potential answers, just not NE or 5-HT)
Squidward was once part of a town filled with other Squidpeople, however, shortly after joining, he is chased out of the group and returns, isolated once again to his home in Bikini Bottom. The Sigma One Receptor empathizes with Squidward’s pain because it too was once part of a community: the opioid receptors. That is, until it was removed from the classification for not binding these opioid antagonists.
What are Naloxone and Naltrexone?
(Su et. al 2009) (S2 ep26)
The number of transmembrane domains in wild type EAATs
What is 8?
The number of bones in the human body
What is 206?
Ketamine, an uncompetitive antagonist, has the highest binding affinity and selectivity toward this receptor when administered at low doses.
What is NMDA?
These are the two (known) biochemical cascades initiated by stimulation of TAAR1
What are adenyl cyclase activation (or cAMP accumulation or PKA activation) and RhoA activation
Mr. Krabs is a weird one: his daughter is a whale and his crush Mrs. Puff is a blowfish! He’s not the only odd one though. Sigma Receptors are odd balls that are widely known to chaperone this receptor (1) in the ER and they also somehow seem to share many of the same agonists and antagonists of this receptor (2) on the cell surface! (2 Answers)
What are IP3 Receptors and Phencyclidine (PCP) receptors?
(McCann 2015 & Garces-Ramirez et al. 2011) (S1 ep8 and S1 ep36)
This EAAT isoform was thought to be uniquely localized to the retina
What is EAAT5?
These are the smallest bones in the human body
What are Malleus, Incus, Stapes?
Ketamine's highly selective acute inhibition of this brain region in the limbic center (often referred to as the "anti-reward center" due to its inhibition of the VTA) is thought to be responsible for its antidepressant effect.
What is lateral habenula?
There is only one trace amine associated receptor (TAAR)
What is NO?
(Humans have 6 functional ones (3 non-functional) and fish have over 100)