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CELLULAR PERMEABILITY AND THE REACTION TO INJURY *
Author(s) -
McLean A. E. M.,
Ahmed K.,
Judah J. D.
Publication year - 1964
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1964.tb52563.x
Subject(s) - library science , medical school , citation , medical research , medicine , political science , medical education , computer science , pathology
A few years ago, Judah and colleagues, were working in the same laboratory as Spector and Willoughby, whose papers appear in this monograph (see Page 839 and Page 874, respectively). We became interested in the drugs that they were using to suppress the inflammatory response, and tried them on animals given various hepatotoxins. To our surprise, they worked. Promethazine, in particular, had a most powerful effect in preventing liver necrosis due to thioacetamide (Gallagher et al., 1956). Since then, antihistamines have been found to give protection in carbon tetrachloride poisoning (Rees et a!., 1961), in infection with mouse hepatitis virus, in tissue culture of mouse macrophages, and against attack by mouse hepatitis virus (Vainio e f al., 1962). We found that promethazine and rebated drugs were powerful and specific inhibitors of the active transport of ions (Judah & McLean, 1962). We then tried the classical inhibitors of active transport of the ions-the digitalis alkaloids-to see if they gave protection against liver injury. Both digoxin and ouabain were effective, reducing the cell necrosis and elevation of serum enzyme activity produced by thioacetamide (Judah et al., 1964). We have been working on the enzymlatic basis of ion transport and find that the drugs that inhibit ion transport inhibit the swelling and contraction of mitochondria (Judah, 1961 ), inhibit the sodium and potassium activated ATP-ases, and inhibit the incorporation of phosphlate into phosphoprotein. We find that although all the drugs mentioned inhibit these enzyme systems in all tissues that we have studied, still there is a considerable variation in the sensitivity to drugs. Presumably, this means that while all cells possess the enzymes responsible for ion transport, yet the isoenzymes vary from tissue to tissue; and it is not surprising that we find that ouabain has no effect on the inflammatory response, but is a protective agent and an effective inhibitor of active transport in liver. We have a tenous chain of connectlion between drugs that exert effects that are anti-inflammatory, anti-“cell necrosis,” and anti-ion transport. Where is the common factor?