@article {FEINSTEIN840, author = {M. B. FEINSTEIN and M. VOLPI and S. PERRIE and A. MAKRIYANNIS and R. I. SHA{\textquoteright}AFI}, title = {Mechanisms of Local Anesthetic Action on the Permeability of Erythrocytes, Leukocytes, and Liposomes Containing the Erythrocyte Anion Channel Protein}, volume = {13}, number = {5}, pages = {840--851}, year = {1977}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The local anesthetics tetracaine and dibucaine produce complex effects on the permeability of human erythrocytes and rabbit polymorphonuclear leukocytes. Red cell permeability to small hydrophilic nonelectrolytes (i.e., urea), which probably cross the membrane through water-filled transmembrane protein channels, is unaffected or slightly inhibited by dibucaine (0.5 mM). However, larger, more lipophilic, and less permeable nonelectrolytes (i.e., isopropylurea, butanetriol, triethylene glycol, and tetraethylene glycol) are rendered more permeable by dibucaine (and tetracaine). These effects are probably related to the anesthetic-induced increase in membrane lipid fluidity. Leukocytes exhibit much lower water and urea permeability than red cells, indicating a paucity of hydrophilic channels in the membrane. Dibucaine strongly inhibits urea and methylurea permeability in leukocytes. Thiourea, which is more permeable and lipid-soluble, and which probably diffuses through the membrane lipid domain, was unaffected by dibucaine. Anion transport in erythrocytes procedes by way of a specific membrane-spanning protein, band 3 protein. Dibucaine and tetracaine inhibit SO4= transport noncompetitively over the same concentration range (0.05-1.0 mM) at which they protect red cells against hypotonic lysis. The inhibition of SO4= transport cannot be attributed to a generalized increase in membrane lipid fluidity. Band 3 protein-mediated SO4= transport was also demonstrated in liposomes in which the protein was incorporated into the lipid membrane. Dibucaine and tetracaine increased SO4= transport somewhat in purely lipid membranes, but strongly inhibited band 3 protein-mediated transport. These results demonstrate that anesthetics can block the function of a protein known to be a specific membrane ion channel. It remains to be determined whether the anesthetics interact directly with the protein itself or affect it by altering those lipids in immediate association with the SO4= channels.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/13/5/840}, eprint = {https://molpharm.aspetjournals.org/content/13/5/840.full.pdf}, journal = {Molecular Pharmacology} }