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.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Brown EM,Butters R,Katz C,Kifor Odoi
10.1210/endo-128-6-3047subject
Has Abstractpub_date
1991-06-01 00:00:00pages
3047-54issue
6eissn
0013-7227issn
1945-7170journal_volume
128pub_type
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