Rapid nongenomic steroid action a new age

The TSH receptor is formed as one polypeptide chain and inserted into the thyroid cell plasma membrane. It undergoes a processing that is reminiscent of that occurring with insulin. A segment of 30 or more amino acids is cut out of the receptor at approximately residue 320, forming a two peptide structure with the chains held together by disulfide bonds. It is thought that both the intact and the processed receptor are functional. The processing of the receptor is thought to involve a matrix metalloprotease-like enzyme cleaving the 120 kDa precursor to form the heterodimeric receptor. Subsequently, reduction of the disulfide bonds by a protein disulfide isomerase may separate the two molecules and lead to shedding of the “alpha” subunit. It is an interesting concept that shedding of the alpha subunit might be intimately related to onset of autoimmunity against the TSH receptor. Shedding of the receptor is augmented by TSH stimulation of thyroid cells (58). The amino-terminal ectodomain of the human TSH receptor has been expressed on the surface of CHO cells as a glycosylphosphatidylinositol-anchored molecule. This material can be released from the cells and is biologically active in that it binds immunoglobulins from serum of patients with Graves’ disease, and displays saturable binding of TSH (46), indicating that all of the “immunologic information” related to production of antibodies resides in the extracellular portion of TSH-R.

The structure of cyclocreatine is fairly flat (planar), which aids in passive diffusion across membranes. It has been used with success in an animal study, where mice suffered from a SLC6A8 (creatine transporter at the blood brain barrier) deficiency, which is not responsive to standard creatine supplementation. [98] This study failed to report increases in creatine stores in the brain, but noted a reduction of mental retardation associated with increased cyclocreatine and phosphorylated cyclocreatine storages. [98] As demonstrated by this animal study and previous ones, cyclocreatine is bioactive after oral ingestion [98] [99] and may merely be a creatine mimetic, able to phosphorylate ADP via the creatine kinase system. [98]

Rapid nongenomic steroid action a new age

rapid nongenomic steroid action a new age


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