title: Neomycin mimics the effects of high extracellular calcium concentrations on parathyroid function in dispersed bovine parathyroid cells.
abstract: We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells. Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30 microM. Maximal inhibition (with 200 microM neomycin) was not additive with the suppressive effects of high (2 mM) Ca++. Neomycin also inhibited dopamine-stimulated cAMP accumulation by 90-98% at 100-200 microM, with a half-maximal effect at 40-50 microM. This action was reversible and was blocked by preincubating the cells overnight with 0.5 microgram/ml pertussis toxin. In addition to its suppressive effects on cAMP metabolism and PTH release, neomycin stimulated the accumulation of inositol phosphates and produced a transient increase in the cytosolic Ca++ concentration (Cai) in fura-2-loaded parathyroid cells. The neomycin-evoked spike in Cai persisted despite removal of extracellular Ca++, indicating that it arises from intracellular Ca++ stores. Exposure of cells to elevated magnesium (Mg++) concentrations elicited a similar spike in Cai but blocked the spike in Cai in response to subsequent addition of neomycin and vice versa. Thus, Mg++ and neomycin mobilize Ca++ from the same intracellular store(s). These results indicate that a polycation, neomycin, closely mimics the effects of polyvalent cations on parathyroid function, suggesting that both agents regulate parathyroid function via similar biochemical pathways.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Butters
authors.forename: C
authors.initials: C
authors.lastname: Katz
authors.forename: O
authors.initials: O
authors.lastname: Kifor
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology*; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000166:cytology / Q000502:physiology*; D010281:Parathyroid Hormone / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D000242:Cyclic AMP; D009355:Neomycin; D002118:Calcium; D004298:Dopamine