The effects of metabolic inhibition on uterine metabolism and intracellular pH in the rat.
1. Uterine metabolism was studied in pregnant and non-pregnant rats by measuring high energy phosphates and intracellular pH (with 31-phosphorus nuclear magnetic resonance (31P NMR) spectroscopy) and lactic acid efflux. Isolated, superfused uteri were investigated during control conditions (30 degrees C) and in the presence of metabolic inhibitors and high [K+]. 2. In control conditions the ratio of phosphocreatine and ATP concentrations ([PCr]/[ATP]) was higher in the pregnant (0.88 +/- 0.09) than the non-pregnant uterus (0.52 +/- 0.04). When oxidative phosphorylation was inhibited by cyanide, there was a significant (P less than 0.01) decrease in [PCr] and [ATP] and an increase in the concentration of inorganic phosphate ([Pi]). These changes were greater in the non-pregnant than the pregnant uterus. 3. There was no difference in the mean value of resting pHi found in pregnant and non-pregnant uterus (7.19 +/- 0.04 and 7.17 +/- 0.03, external pH 7.4, n = 10 and 12 respectively). There was a significant intracellular acidification in both pregnant (0.31 +/- 0.04 pH unit) and non-pregnant (0.27 +/- 0.02 pH unit) uterine tissue in the presence of cyanide. These effects of cyanide on metabolites and pHi were fully reversed upon return to control solutions. 4. When both aerobic and anaerobic glycolysis were blocked by iodoacetate, there was a rapid disappearance of high energy phosphates from the 31P NMR spectrum and a large increase in the phosphomonoester spectral region, where sugar phosphate intermediates of glycolysis resonate. These changes were seen in both pregnant and non-pregnant uteri and were irreversible. 5. Lactate production was detected, in the presence of oxygen, in both pregnant and non-pregnant preparations (0.43 +/- 0.07 and 0.25 +/- 0.09 mumols g-1 min-1, respectively). In both preparations the rate of lactate production was markedly increased in the presence of cyanide. The increase was much more marked in non-pregnant (approximately 10-fold) than pregnant (approximately 5-fold) uteri, resulting in a very similar rate of lactate efflux in cyanide. 6. When lactate efflux in non-pregnant uteri was blocked by alpha-cyano-4-hydroxycinnamate, there was a significant acidification (0.21 +/- 0.04 pH unit, n = 6). The addition of cyanide produced a more pronounced acidification (0.34 +/- 0.04 pH unit) than that seen with either cyanide or alpha-cyano-4-hydroxycinnamate alone.(ABSTRACT TRUNCATED AT 400 WORDS)
Wray
S
S
Department of Physiology, University College London.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D000963:Antimetabolites; D003373:Coumaric Acids; D003486:Cyanides; D007461:Iodoacetates; D007773:Lactates; C007175:alpha-cyano-4-hydroxycinnamate; D019344:Lactic Acid; D011188:Potassium; D019807:Iodoacetic Acid