Alpha-aminoisobutyric acid transport in rat soleus muscle and its modification by membrane stabilizers and insulin.
The non-metabolizable amino acid alpha-aminoisobutyric acid (AIB) has been used to study the effects of insulin and a number of membrane stabilizers on amino acid transport in rat soleus muscle in an attempt to characterize the mechanisms present. 2. Insulin (5--100 millimicron./ml) increases the net uptake of AIB two- to threefold. Since insulin is without significant effects on AIB efflux, stimulation of net uptake appears to result directly from an increased AIB influx. 3. All classes of membrane stabilizer tested affected AIB fluxes but the responses observed varied for different classes of compounds. 4. The total anaesthetic, tetracaine, reduced AIB accumulation both in the absence and presence of insulin by a similar proportion. The effects on AIB efflux were dependent on the concentration of tetracaine used. Efflux was suppressed by concentrations up to 1 mM whereas 4 mM-tetracaine caused a massive stimulation of AIB efflux. Other local anaesthetics and barbiturates produced similar effects. 5. Another group of membrane stabilizers, exemplified by chlorpromazine, also suppressed AIB uptake, but at no concentration did they reduce AIB efflux. In fact, efflux of AIB began to be increased at concentrations of chlorpromazine which were giving only a modest inhibition of uptake. 6. Measurement of the initial rate of uptake showed that it involved two components. Tetracaine appears to inhibit the saturable component whilst leaving the non-saturable component relatively unaffected. 7. The active uptake of AIB was shown to be Na+-dependent, and under Na+-free conditions tetracaine had no effect on the initial rate of uptake. The non-saturable component was also shown to be Na+-sensitive, uptake from high extracellular concentrations of AIB being reduced in Na+-free media. 8. The possibility of the presence of a carrier-mediated AIB efflux mechanism was investigated. AIB efflux was stimulated by extracellular AIB (homo-exchange) or glycine (hetero-exchange), but not mannitol. This suggests the involvement of a carrier-mediated process in AIB efflux. 9. The present study has demonstrated a heterogeneity among different classes of membrane stabilizers in their actions on AIB efflux which is in marked contrast to previous observations of sugar and cation transport in this preparation. Possible reasons for these differences are discussed.
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013748:Tetracaine / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D007328:Insulin; D013748:Tetracaine; D013874:Thiopental; D002746:Chlorpromazine