Mechanisms of mercurial and arsenical inhibition of tyrosine absorption in intestine of the winter flounder Pseudopleuronectus americanus.
Effects of HgCl2 (100 microM) para-chloromercuribenzene sulfonate (PCMBS) (1 mM), and oxophenylarsine (OPA) (250 microM) were determined on (a) the rate of Na pump activity in intact winter flounder intestine; (b) activity of Na-K-ATPase in tissue homogenates; and (c) Na-dependent and Na-independent uptake of tyrosine in brush border membrane vesicles. Initial rate of uptake (influx) of 86Rb from the serosal solution of tissues mounted in Ussing chambers, a measure of Na-K-ATPase activity in the intact cell, was inhibited by all three agents with differing time courses. Rapidly permeating HgCl2 inhibited influx to the same degree as ouabain at 30 min, whereas the effects of PCMBS and OPA required 90 min. Cell potassium was also measured as an indirect indicator of ATPase activity and cell membrane permeability. All three agents decreased cell K, although effects on cell K lagged behind those for inhibition of the ATPase. At the concentrations used in the Ussing chamber (or at one-tenth concentration), all agents completely inhibited Na-K-ATPase activity in enzyme assays performed with tissue homogenates. In contrast, only HgCl2 decreased Na-dependent uptake of tyrosine by brush border membrane vesicles. These results suggest that mercurial and arsenical effects on tyrosine absorption are due to inhibition of the Na-K-ATPase thus decreasing the driving force for the cellular uptake by the Na-tyrosine cotransport system. Direct effects on Na-tyrosine cotransport may play a role in the inhibition observed with HgCl2, but not for PCMBS or OPA.
Musch
M W
MW
Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672.
Chauncey
B
B
Schmid
E C
EC
Kinne
R K
RK
Goldstein
L
L
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D020261:Arsenic Poisoning; D001152:Arsenicals / Q000494:pharmacology; D005412:Flatfishes / Q000378:metabolism*; D005432:Flounder / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008627:Mercuric Chloride / Q000494:pharmacology / Q000633:toxicity*; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D010663:Phenylmercury Compounds / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D001152:Arsenicals; D010663:Phenylmercury Compounds; D012414:Rubidium Radioisotopes; C029341:oxophenylarsine; D014443:Tyrosine; D008627:Mercuric Chloride; D002731:4-Chloromercuribenzenesulfonate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium