Effects of weak bases on the degradation of endogenous and exogenous proteins by rat yolk sacs.
In rat yolk sacs incubated in vitro, the rates of degradation of endogenous [3H]leucine-labelled proteins and of pinocytically ingested 125I-labelled bovine serum albumin were both decreased in the presence of either ammonium, methylammonium or ethylammonium ions (0-20 mM) or much lower concentrations of chloroquine (0-500 microM). These effects were also accompanied by an inhibition of pinocytosis, as measured by the rate of uptake of 125I-labelled polyvinylpyrrolidone, and by a fall in the [ATP]/[ADP] ratio within the tissue. Re-incubation in inhibitor-free medium of yolk sacs previously exposed to a weak base restored pinocytic and proteolytic capacities, except for tissues exposed to chloroquine at concentrations above 0.1 mM (these appeared to be cytotoxic); an attendent rise in [ATP]/[ADP] ratios to near normal values was also observed. Weak bases, at concentrations that fully arrested the breakdown of 125I-labelled albumin, failed to inhibit by more than 45% the degradation of [3H]leucine-labelled endogenous proteins. Since 125I-labelled bovine serum albumin has been shown to be degraded entirely intralysosomally by yolk sacs, this suggests either that the hydrolysis of endogenous proteins is shared between lysosomes and some other site or that, unlike 125I-labelled albumin, some endogenous proteins can be degraded within lysosomes at abnormally high pH.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D010873:Pinocytosis / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism*
D000227:Adenine Nucleotides; D008565:Membrane Proteins; D000644:Quaternary Ammonium Compounds; D012710:Serum Albumin, Bovine; D002738:Chloroquine