Nicotinic agonists regulate alpha-bungarotoxin binding sites of TE671 human medulloblastoma cells.
The TE671 human medulloblastoma cell line expresses a variety of characteristics of human neurons. Among these characteristics is the expression of membrane-bound high-affinity binding sites for alpha-bungarotoxin, which is a potent antagonist of functional nicotinic acetylcholine receptors on these cells. These toxin binding sites represent a class of nicotinic receptor isotypes present in mammalian brain. Treatment of TE671 cells during proliferative growth phase with nicotine or carbamylcholine, but not with muscarine or d-tubocurarine, induced up to a five-fold increase in the density of radiolabeled toxin binding sites in crude membrane fractions. This effect was blocked by co-incubation with the nicotinic antagonists d-tubocurarine and decamethonium, but not by mecamylamine or by muscarinic antagonists. Following a 10-13 h lag phase upon removal of agonist, recovery of the up-regulated sites to control values occurred within an additional 10-20 h. These studies indicate that the expression of functional nicotinic acetylcholine receptors on TE671 cells is subject to regulation by nicotinic agonists. Studies of the murine CNS have consistently indicated nicotine-induced up-regulation of nicotinic acetylcholine receptors, thereby supporting the identification of the toxin binding site on these cells as the functional nicotinic receptor. Although a mechanism for this effect is not apparent, nicotine-induced receptor blockade does not appear to be involved.
Siegel
H N
HN
Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013.
Lukas
R J
RJ
D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D003650:Decamethonium Compounds / Q000494:pharmacology; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D009116:Muscarine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014403:Tubocurarine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002038:Bungarotoxins; D003650:Decamethonium Compounds; D011978:Receptors, Nicotinic; D009538:Nicotine; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; C033019:decamethonium; D014403:Tubocurarine