Psoriasis: a new innovative approach
There is new innovative approach for Psoriasis. Pruritus is an important symptom in psoriasis. Gamma aminobutyric acid (GABA) is an important neurotransmitter that regulates neuronal excitability in the nervous system.
The GABA receptors (R) are classiﬁed into GABA, GABA and GABA types. The GABA ligand and its GABAA R may play a role for the pathogenesis of psoriasis. Unmyelinated afferent nerves of skin have GABA A R, reported for cat, which have been shown to enhance nociceptive signals upon stimulation with GABA agonists.
Inﬂammation is an important part of psoriatic lesions
Functional GABAA receptors (R) exist in certain inﬂammatory cells, such as CD4+ T cells and macrophages. Where they act as inhibitors of antigen-speciﬁc T cell proliferation. And also as inhibitors of the production of interleukin (IL)-6, IL-12, inducible nitric oxide (iNOS), IL- 1b, and tumor necrosis factor (TNF)-a.
GABAA R agonists have been shown to accelerate cutaneous recovery and prevent epidermal hyperplasia in wounds in mouse skin. And suppress wound-induced cutaneous inﬂammation.
The binding site for benzodiazepines is distinct from the binding site for barbiturates and GABA on the GABAA receptor, and also produces different effects on binding.
With the benzodiazepines causing bursts of chloride channel opening to occur more often, while the barbiturates cause the duration of bursts of chloride channel opening to become longer.
Dosage strictly controlled
Since these are separate modulatory effects, they can both take place at the same time. And so the combination of benzodiazepines with barbiturates is strongly synergistic, and can be dangerous if dosage is not strictly controlled.
There were inﬂammatory cells immune reactive for the GABA ligand. Mostly in the papillary dermis, their number being increased (P <0.01) in the involved skin, 22.0 ± 26.8 cells per section. In comparison to the non involved skin, 1.8 ± 1.8, and normal control skin, 0.8 ± 0.8.
There is an increase (P < 0.01) in the number of inﬂammatory cells stained positive for the GABAA R in the involved skin, 33.9 ± 39.9 cells per section. Most of which were located in the papillary dermis, compared to the non-involved skin, 0.3 ± 0.3, and normal skin, 0.1 ± 0.2.
There was a positive correlation when comparing GABA ligand (R = 0.63; P = 0.05) and GABAA R (R = 0.66; P < 0.05) positive inﬂammatory cells in involved skin. Respectively, with pruritus cells stained for the GABA ligand and the GABAA R in involved skin of psoriatic patients.
GABA and GABAA R
This study has demonstrated an increase in the number of cells stained for the GABA ligand and the GABAA R in involved skin of psoriatic patients. This suggests a role for these molecules in the pathogenesis of this disease and as targets for new therapeutic approaches.
In a recent study reported an improvement in psoriasis following treatment with GABA analogues Gabapentin and pregabalin macrophages in psoriasis. TNF-a release from macro- phages is inhibited by GABA , which suggests that partial macro phage induced psoriasis development and maintenance can be prevented by a GABA ligand.
It has been shown that oral Pregabalin can alleviate chronic pruritus due to polycythemia vera. Both GABA alpha and beta sub units bind barbiturates but only the alpha sub unit binds benzodiazepines; both benzodiazepines and barbiturates act to increase the GABA induced Cl current.
GABA type B receptor uses a G protein as a secondary messenger; Baclofen is a type B agonist. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABA ergic effect, barbiturates also block the AMPA receptor, a sub type of glutamate receptor.
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