What is the cannabinoid autoreceptor?

Question

"Is there a cannabinoid autoreceptor? And if so what is the cannabinoid autoreceptor?"

(i.e. is the cannabinoid autoreceptor CB₁, CB₂ or is it one of the G protein coupled receptors, GPR18, GPR55 or GPR119?)

Where:

• An autoreceptor is a receptor located presynaptically that sends back negative feedback that inhibits the synthesis of the neurotransmitter to which the autoreceptor belongs and this negative feedback also inhibits the release of the neurotransmitter from storage vesicles into the synaptic cleft.

• The CB₁ and CB₂ receptors are respectively called the first and second cannabinoid receptors and are a pair of G protein coupled receptors.

• GPR18, GPR55 and GPR119 are G protein coupled receptors that are also activated by some lipid messengers including a few of the endocannabinoids and their related compounds.

Answer 1

CB1 and CB2 are indeed particular genes which are present in neurons, but also liver and other tissues. The HGNC website is a good resource for questions like this - HGNC is the international organization that tries to unify and track gene names.

The official gene names are CNR1 and CNR2 respectively. Gene names are a bit of a mess, since many genes have been found by different experiments and so have many names.

CNR1 has other aliases, I see: CANN6, CB-R, CB1, CB1A, and CB1K5.

CNR2 has only the one alias: CB2.

I also searched the HGNC website for those alternate gene symbols and they appear to be different genes, although CB1 and CB2 are GPCR class receptors, humans have hundreds of these genes. Most cell scientists would not be surprised if cannabinols bound other receptors - the fact is probably only that CB1 and CB2 bind strongest and were found first. Often weak binding is important to specific pharma/neuro responses.

That is to say there shouldn't be any single Cannabinoid receptor in the animal repetoire. CB1 and CB2 almost certainly have a primary function other than cannibinol binding. Primates evolved in the old world and cannabis is thought to have originated in the Himalayan regions. From an evolutionary standpoint, the activity of cannabinoids is as much coincidence as anything, so you would expect that a single receptor gene is unlikely.