Glycine receptors (GlyR)

Glycine receptors (GlyR) are found in the spinal cord, brainstem, midbrain, sensory systems (retina), and in some higher brain areas, such as the hippocampus.They provide inhibitory neurotransmission and are implicated in the coordination of reflex responses, processing of sensory signals, and pain sensation.It has been identified that mutations in the gene encoding the neurotransmitter-binding subunit of GlyR underlie the molecular basis of hyperekplexia and spastic and oscillatory neurogenetic disorders.

B0084-008878
β-Alanine
107-95-9
Sarcosine
107-97-1
Hypotaurine
300-84-5

Background


An overview of glycine receptors (GlyR)

The glycine receptor (GlyR) is the first neurotransmitter receptor protein isolated from the mammalian central nervous system, comprising two polypeptide chains, the α-subunit and the β-subunit. The adult GlyR is a pentamer of three α-subunits and two β-subunits. The GlyRs are found in the spinal cord, brainstem, midbrain, sensory systems (retina), and in some higher brain areas, such as the hippocampus. They provide inhibitory neurotransmission and are implicated in the coordination of reflex responses, processing of sensory signals, and pain sensation. It has been identified that mutations in the gene encoding the neurotransmitter-binding subunit of GlyR underlie the molecular basis of hyperekplexia and spastic and oscillatory neurogenetic disorders.

Inhibition of glycine receptors (GlyR)

Strychinen is currently known to be the highest-specificity, most powerful GlyR antagonist, and it has been reported that a steroidal analogue. RU5135 is also a strong antagonist of GLyR. In addition, picrotoxin is a chlorine channel blocker, and its ability to block the induction reaction formed by the homopolymerization subunitα1 of GlyR is much stronger than that of GlyR formed by isopolymerization subunitαand β.

Glycine receptors (GlyR) and diseases

Mutations in GlyR can lead to some serious dyskinesia disorders. For example, a dominant genetic disease of humans, hyperekplexia, whose etiology is the mutation of the gene encoding of the GlyRα1 subunit, that is, R271 in the extracellular ring between M2 and M3 is replaced by leucine/glycine. The affinity between glycine and the mutant receptor decreases, while the affinity of the strychnine is not affected. Taurine and beta-alanine bind to receptors normally, but combined channels are not open after the combination. So the R271 plays a key role in coupling agonist binding and channel opening. Glycine can regulate the normal spinal reflex, muscle tension and motor neuron discharge during exercise, so once glycine-induced current amplitude decreases, it will directly lead to muscle movement over or uncontrolled, showing the mischief phase, shrug, clenched fists, Limbs violently twitching and others.