Membrane transport of clindamycin in alveolar macrophages
| Autor: | N L King-Thompson, W L Hand |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
Biological Transport
Active Biology Absorption Microbiology Cell membrane chemistry.chemical_compound medicine Extracellular Animals Pharmacology (medical) Pharmacology Adenosine transport Clindamycin Macrophages Cell Membrane Membrane transport Pulmonary Alveoli Kinetics Infectious Diseases medicine.anatomical_structure chemistry Puromycin Antibiotic transport Rabbits Intracellular Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 21:241-247 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.21.2.241 |
| Popis: | The use of antibiotics which can penetrate phagocytic cells and kill intracellular organisms is desirable in the treatment of chronic facultative bacterial infections. Recently, we reported that several antibiotics were selectively concentrated by rabbit alveolar macrophages. Clindamycin accumulation was especially marked. In the present study we evaluated the plasma membrane transport (initial uptake) of clindamycin in alveolar macrophages. The transport of clindamycin is an active process, as documented by requirements for cellular viability, elevated environmental temperature, metabolic energy, and establishment of the 40- to 50-fold cellular/extracellular gradient. Energy for membrane transport of the drug depended at least in part upon mitochondrial oxidative respiration and cell membrane Na-K pump activity. Kinetic analysis of active clindamycin transport revealed it to be saturable, with a high binding affinity (Km = 1 mM) and a high velocity of uptake (Vmax = 15.8 nmol/45 s per 10(6) cells). Clindamycin uptake was not influenced by the presence of hexose or amino acids, but was inhibited by nucleosides (adenosine, puromycin). Decreased clindamycin transport in the presence of puromycin was typical of competitive inhibition (increased Km, unchanged Vmax). Conversely, competitive inhibition of adenosine transport by clindamycin was documented. Thus, clindamycin is transported into alveolar macrophages via the nucleoside system. The potential biological consequences of this unique antibiotic transport mechanism are of interest. |
| Databáze: | OpenAIRE |
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