Linked Life Data

1322287

Source:http://linkedlifedata.com/resource/pubmed/id/1322287

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-9-2
pubmed:abstractText
We previously showed that the polycationic aminoglycoside antibiotic neomycin mimics the effects of high extracellular calcium (Ca2+) concentrations on several aspects of parathyroid function. In the present studies we examined the actions of several additional aminoglycosides on dispersed bovine parathyroid cells to investigate the relationship between antibiotic structure and function in eliciting Ca(2+)-like effects on intracellular second messengers and PTH release. Of the antibiotics tested, those with six amino groups (neomycin-B and -C) were most potent in inhibiting dopamine-stimulated cAMP accumulation, showing IC50 values (the concentration producing a half-maximal inhibitory effect) of 7.7 x 10(-5) and 1.5 x 10(-4) M. Gentamicin-C, paromomycin, and tobramycin, which have five amino groups, were less potent, with IC50 values of 4 x 10(-4), 10(-3), and 3.3 x 10(-4) M, respectively, while gentamicin-B, kanamycin, and ribostamycin, with four amino groups, were least potent (respective IC50 values, 2.0, 2.9, and 3 x 10(-3) M). These antibiotics showed a similar order of potency for inhibiting PTH release, with a close correlation between their IC50 values for modulating cAMP accumulation and PTH release (r = 0.98; P less than 0.001). Finally, they showed qualitatively similar potencies for eliciting transient increases in the cytosolic free Ca2+ concentration arising from the release of Ca2+ from intracellular stores. Neomycin-B and -C both acted at 10(-4) M; gentamicin-C, paromomycin, and tobramycin evoked free intracellular Ca2+ spikes at 1.4 x 10(-4) to 6.3 x 10(-4) M; and gentamicin-B, kanamycin, and ribostamycin had little or no effect at 7 x 10(-4) M, the highest concentration tested. Thus, a variety of aminoglycoside antibiotics mimic the effects of Ca2+ and other polyvalent cations on parathyroid function. Their relative potencies are closely related to the total number of amino groups on the molecule, with a 5- to 6-fold increase in potency for each additional amino group between four and six.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
903-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Structure-function relationships for the effects of various aminoglycoside antibiotics on dispersed bovine parathyroid cells.
pubmed:affiliation
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.