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Induction and inhibition of pinocytosis by aminoglycoside antibiotics
Author(s) -
Johansson P.,
Josefsson J.O.,
Nässberger L.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16215.x
Subject(s) - aminoglycoside , pinocytosis , antibiotics , microbiology and biotechnology , pharmacology , medicine , biology , chemistry , endocytosis , receptor
1 We investigated whether differences in induction or stimulation of pinocytosis by six aminoglycosides reflected reported differences in their nephrotoxicity. Pinocytosis induced by antibiotics, Na + , K + or Ca 2+ was quantified by the number of pinocytotic channels in Amoeba proteus , a cell suitable for the study of the pinocytotic process. 2 The aminoglycosides were potent inducers of pinocytosis. They were effective in the order of their cationic charge: neomycin > gentamicin > netilmicin = tobramycin > kanamycin > streptomycin. Factors which reduced the charge of the molecules, i.e. alkaline pH and combination with carbenicillin or heparin, diminished pinocytosis. 3 Like La 3+ the antibiotics inhibited Na + ‐induced pinocytosis. The order of efficacy was netilmicin > gentamicin > neomycin. A similar rank order, which is the reverse of the order of nephrotoxicity, was observed for inhibition of Ca 2+ ‐stimulated, Na + ‐induced pinocytosis. Netilmicin was also the most potent inhibitor of the Ca 2+ ‐induced pinocytosis in cells treated with concanavalin A. Inhibition of Ca 2+ ‐stimulated pinocytosis by netilmicin was reversed by Ca 2+ , the calcium ionophore A 23187, or 4‐aminopyridine. 4 We have shown that several nephrotoxic cations are strong inducers of pinocytosis in the amoeba, that aminoglycosides in Ringer solution induce pinocytosis in the approximate order of their nephrotoxicity and that factors which are known to diminish toxicity reduce pinocytosis. It, therefore, appears that the mechanism of aminoglycoside nephrotoxicity is related to their ability to induce pinocytosis in the amoeba. Low inducing potency and strong Ca 2+ ‐antagonism, as for netilmicin, are qualities which may reduce the tendency of polycationic compounds to damage proximal tubular cells.