Effects of antibiotics on uptake of calcium into isolated nerve terminals.
The goal of the present study was to determine whether several antibiotics which are known to block neuromuscular transmission would impair depolarization-dependent and/or -independent uptake of calcium into isolated nerve terminals prepared from forebrain synaptosomes of rats by conventional methods. Antibiotics tested for potential block of Ca++ uptake included the aminoglycosides neomycin and streptomycin, the lincosamide clindamycin, oxytetracycline and polymyxin B. Drugs were applied in concentrations ranging from 1 to 1000 microM. Uptake of 45Ca was determined during depolarization induced by an elevated K+ concentration (77.5 mM). Influxes of 45Ca during 1 and 10 sec of depolarization were used to assess Ca++ uptake via a "fast, inactivating path" and total uptake, respectively. Uptake of 45Ca during 10 sec of depolarization into synaptosomes which were previously depolarized for 10 sec in the presence of 77.5 mM K+ but in the absence of external Ca++ was used to measure uptake during a "slow, noninactivating path." Total depolarization-dependent uptake of 45Ca was depressed significantly by all antibiotics tested except oxytetracycline; however, the various agents differed with respect to their efficacy and potency as blockers of Ca influx. The fast component of uptake, which is thought to be associated with neurotransmitter release, was decreased significantly by all antibiotics. Neomycin and polymyxin were the most potent and most effective at lowering fast phase 45Ca influx; streptomycin, was intermediate in effectiveness whereas clindamycin and oxytetracycline were only effective at concentrations greater than or equal to 100 microM. Only clindamycin, streptomycin and polymyxin B caused significant reductions in the "slow" phase of 45Ca uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Atchison
W D
WD
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Adgate
L
L
Beaman
C M
CM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002981:Clindamycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D009355:Neomycin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010118:Oxytetracycline / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D000900:Anti-Bacterial Agents; D002132:Calcium Radioisotopes; D002981:Clindamycin; D009355:Neomycin; D011112:Polymyxin B; D002118:Calcium; D010118:Oxytetracycline