Nerve growth factor induces 5-HT3 recognition sites in rat pheochromocytoma (PC12) cells.
In rat pheochromocytoma (PC12) cells, nerve growth factor (7S NGF) induced the expression of recognition sites that bind the specific 5-HT3 antagonist (S-) [3H]zacopride. Culturing PC12 cells for 8-12 days in the presence of 50 ng/ml NGF increased the density (Bmax) of (S-) [3H]zacopride binding sites in cell membranes (0-100,000 x g fraction) from 0 to 105 fmoles/mg protein. This binding exhibited high affinity for (S-) [3H]zacopride (Kd = 0.8 nM), was specific (greater than 95%), and was inhibited by 5-HT3 compounds with a rank of potency (quipazine greater than ICS 205-930 greater than GR38032F greater than BRL24924 approximately MDL 72222 greater than phenylbiguanide greater than or equal to serotonin greater than 2-methyl-serotonin greater than metoclopramide) which was distinct from neuroblastoma cells. Thus, NGF-differentiated PC12 cells possess a 5-HT3 receptor and should be useful to investigate its regulation and biochemical mechanism of action.
Gordon
J C
JC
Department of Molecular Biology, A.H. Robins Research Laboratories, Richmond, VA 23261-6609.
Rowland
H C
HC
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D012044:Regression Analysis; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D009414:Nerve Growth Factors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C055971:zacopride