Inhibition by steroids of the uptake of potassium by capillaries isolated from rat brain.

The effect of steroids on the uptake and release of K+ by capillaries isolated from rat brain was investigated. 86Rb’ uptake was used as a transport analog of K+. The uptake of 86Rb’ by the capillaries was markedly inhibited by ouabain. The ouabain sensitive fraction of 86Rb’ uptake was inhibited by corticosterone with an 150 of 8 X 10m4M. Inhibition was immediate in onset and rapidly reversible after removal of the steroid. Corticosterone did not alter the affinity of the transport carrier for K+ or the passive efflw of ‘6Rb’ from the capillaries. Other steroids inhibited ouabain sensitive %Rb+ uptake in relation to their lipid solubihty. These features suggest a direct membrane action for high dose steroid therapy, possibly on Na+,K+-ATFase, rather than a nuclear mediated change in cell In addition to their well-known interaction with high affinity receptors in target cells [l], steroids may produce pharmacological responses by direct action on cellular membranes and enzymes 12-41. A direct action is more likely to be the mechanism when very high doses of steroid are required for a therapeutic response, as is found in the treatment of brain edema following head injury [5,6]. The endothelial cells in brain capillaries are involved in the formation of this type of brain edema [7,8] and are a possible site for the beneficial action of high dose steroid therapy. It has recently become possible to isolate metabolically active brain capillaries that are suitable for study of drug interactions. The uptake of potassium by isolated brain capillaries is mediated by Na+,K+ATPase [9, lo]. The activity of this enzyme is linked to fluid secretion in other barrier tissues [ll]. Since an alteration in fluid secretion by brain capillaries may be important to the formation or resolution of brain edema, we investigated the effect of steroids upon this process. We found that steroids inhibit the uptake but not the release of potassium by isolated brain capillaries.