Evidence for thymopoietin and thymopoietin/alpha-bungarotoxin/nicotinic receptors within the brain.
Thymopoietin, a polypeptide hormone of the thymus that has pleiotropic actions on the immune, endocrine, and nervous systems, potently interacts with the neuromuscular nicotinic acetylcholine receptor. Thymopoietin binds to the nicotinic alpha-bungarotoxin (alpha-BGT) receptor in muscle and, like alpha-BGT, inhibits cholinergic transmission at this site. Evidence is given that radiolabeled thymopoietin similarly binds to a nicotinic alpha-BGT-binding site within the brain and does so with the characteristics of a specific receptor ligand. Thus specific binding to neuronal membranes was saturable, of high affinity (Kd = 8 nM), linear with increased tissue concentration, and readily reversible; half-time was approximately 5 min for association and 10 min for dissociation. Binding of 125I-labeled thymopoietin was displaced not only by unlabeled thymopoietin but also by alpha-BGT and the nicotinic receptor ligands d-tubocurarine and nicotine; various other receptor ligands (muscarinic, adrenergic, and dopaminergic) did not affect binding of 125I-labeled thymopoietin. Thymopoietin was shown by ELISA to be present in brain extracts, displacement curves of thymus and brain extracts being parallel to the standard thymopoietin curve, and Western (immuno) blot identified in brain and thymus extracts a thymopoietin-immunoreactive polypeptide of the same molecular mass as purified thymopoietin polypeptide. We conclude that thymopoietin and thymopoietin-binding sites are present within the brain and that the receptor for thymopoietin is the previously identified nicotinic alpha-BGT-binding site of neuronal tissue.
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Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
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D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002038:Bungarotoxins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D018000:Receptors, Peptide; D013946:Thymopoietins / Q000032:analysis* / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D018000:Receptors, Peptide; D013946:Thymopoietins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C044349:thymopoietin receptor