Does anyone know them so I can search for possible NET mutations in my 23andme data?
The proper annotation for the NET gene is SLC6A2 and according to http://www.ncbi.nlm.nih.gov/gene/6530 it's located between 55689542 and 55740104 on chromosome 16. So the following 23andMe SNPs are included, and probably a few before and after them:Does anyone know them so I can search for possible NET mutations in my 23andme data?
Norepinephrine, also known as noradrenaline, is a neurotransmitter found in the sympathetic nervous system and biosynthesized from the amino acid tyrosine, which is sequentially hydroxylated to generate dihydroxyphenylallanine (Dopa), decarboxylated to produce dopamine, and hydroxylated to form NE (19).
As one of the crucial neurochemical messengers in the CNS, NE plays an important role in human physiology and pathology, and is involved in mood regulation, sleep regulation, expression of behavior and the general degree of alertness and arousal (20). Norepinephrine also exerts central control over the endocrine system and autonomic nervous system. Outside the CNS and adrenal glands, NE is located in the sympathetic nerve endings, and the NE content of a particular tissue reflects the extent of its sympathetic innervation (21).
The NET is located in the plasma membrane of noradrenergic neurons, where it functions to take up synaptically released NE. The NET thus serves as the primary mechanism for the inactivation of noradrenergic signaling (22-24). Reuptake of NE by the NET protein (also known as uptake 1) is the primary mechanism by which the biological effects of NE in the synapse are terminated (Fig. 2). The inactivation process through the NET is critical in preventing an excessive increase in the NE concentrations in the synaptic cleft, which regulate adrenergic neurotransmission in the brain, as well as the removal of NE from the heart and other peripheral organs (21, 25). Reuptake of NE is competitive with a variety of naturally occurring amines and drugs.
Drugs of abuse (e.g., cocaine) and antidepressants (e.g., desipramine, venlafaxine, reboxetine, bupropion) block the transport of NE and thereby cause an elevation in the synaptic concentrations of NE and potentiation of the activation of postsynaptic receptors (21, 26, 27). The above neurobiology of the NE system and other accumulating evidence support the view that NE plays an important role in the CNS
If the norepinephrine is elevated in the synapses, then that means the existing levels are basically staying the same, but are being used more effectively.Okay Im confused.. when they say somehing like cocaine and antidepressants block to transport of NE and thereby cause an elevation in the synaptic concentrations of NE, does that mean they help lower NE in the body? The whole article is here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518795/ (im really struggling to get my head around things).
Some of us have been doing that, but with much more with this one gene.Maybe we can share results and discover something new.
If the norepinephrine is elevated in the synapses, then that means the existing levels are basically staying the same, but are being used more effectively.
Have you ever had norepinephrine levels tested? There's been a very recent study of ME patients showing that a gene which blocks norepinephrine production is 3x more active after exertion compared to sedentary controls.
Hence if your norepinephrine is low and you have OI symptoms (like me!), the upregulation of that ADRA2A gene could explain it. There are a couple drugs when can help suppress it, thereby raising norepinephrine levels.
Substances which keep norepinephrine in the synapses shouldn't affect norepinephrine levels much.oh now Im even more confused. So this all doesnt affect a persons test result levels at all??
The stuff I said about ADRA2A might not apply to you - you obviously don't want to be repressing the gene which is lowering your norepinephrine levels! There must be something else (additional?) going in the ME patients with hypertensive POTS.Now Im heaps more confused as you've been speaking of the opposite.. can you explain how all the stuff would reate to me ..what is going on with my noradrenaline as far as genes go?