Role of hexose monophosphate shunt in parathyroid hormone secretion.
The metabolism of labeled glucose by collagenase-dispersed bovine parathyroid cells was examined. When the medium calcium ion concentration was increased to 2.0 mM, the rate of 14CO2 release from [1-14C]glucose was increased 169 +/- 45% compared with the rate of 0.5 mM calcium. There was no significant change in the rate of 14CO2 release from [6-14C]glucose by this maneuver. The greatest increase in 14CO2 release and decrease in parathyroid hormone secretion occurred between medium calcium ion concentrations of 0.5-1.5 mM. This difference in the metabolism of glucose represents a true increase in hexose shunt activity because the incorporation of label from either [1-14C]- or [6-14C]glucose into parathyroid tissue lipids was equal. This suggests equilibration of label at the level of triose-phosphates. The increase in hexose shunt activity was not due to a calcium-mediated increase in glucose uptake because calcium changes did not affect 2-[3H]deoxyglucose transport by the cells. Phenazine methosulfate added to cells incubated at 0.5 mM calcium selectively increased hexose shunt activity in a dose-dependent manner (91 +/- 33% overall) and concomitantly inhibited parathyroid hormone secretion 65% overall at 0.5 mM calcium. The compound 6-aminonicotinamide inhibited hexose shunt activity but could not overcome the inhibition of hormone secretion at 2.0 mM calcium. A decrease in protein biosynthesis cannot fully explain the inhibition of hormone secretion by calcium or phenazine methosulfate because [3H]-leucine incorporation into total cell protein was not as affected as secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002245:Carbon Dioxide / Q000032:analysis; D002250:Carbon Radioisotopes; D002417:Cattle; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006600:Hexosephosphates / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011506:Proteins / Q000235:genetics
D002250:Carbon Radioisotopes; D006600:Hexosephosphates; D010281:Parathyroid Hormone; D011506:Proteins; D002245:Carbon Dioxide; D008773:Methylphenazonium Methosulfate; D005947:Glucose; D002118:Calcium