Thymopoietin, a thymic polypeptide, regulates nicotinic alpha-bungarotoxin sites in chromaffin cells in culture.
The identity of the neuronal nicotinic alpha-bungarotoxin (alpha-BGT) site, which appears to be distinct from the functional nicotinic receptor, is unclear. Recent work in our laboratory has shown that the thymus-derived polypeptide thymopoietin potently and specifically interacts at the nicotinic alpha-BGT site in brain. The present results show that thymopoietin also interferes with the binding of 125I-alpha-BGT to chromaffin cells in culture; a dose-dependent inhibition in binding was observed, with an IC50 of 10(-8) M. To assess the long term effect(s) of thymopoietin in nervous tissue, chromaffin cells were exposed to the polypeptide for varying periods of time. Incubation of the cells in culture with thymopoietin (10(-9) to 3 x 10(-7) M) for 2 to 7 days resulted in an approximate 3-fold increase in alpha-BGT binding. Saturation analysis indicated this was due to an increase in the Bmax. The thymopoietin-induced increase in binding could be reversed with nicotine: thus, the sites can be regulated by a nicotinic receptor ligand. Although thymopoietin potently interacted at the nicotinic alpha-BGT receptor, nicotinic receptor responsiveness was not affected after short or long term exposure to the peptide. Neither basal nor nicotinic receptor-stimulated tyrosine hydroxylase activity was altered by thymopoietin. As well, resting and acetylcholine-evoked noradrenaline release remained similar to control after exposure of the cells to the polypeptide. These results indicate that the thymic polypeptide thymopoietin specifically interacts with the nicotinic alpha-BGT receptor population and, furthermore, can regulate the toxin binding sites in chromaffin cells in culture.
Quik
M
M
Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
Afar
R
R
Geertsen
S
S
Audhya
T
T
Goldstein
G
G
Trifaró
J M
JM
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D013946:Thymopoietins / Q000494:pharmacology*; D013951:Thymus Hormones / Q000494:pharmacology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D013946:Thymopoietins; D013951:Thymus Hormones; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine; D009638:Norepinephrine