Relationship of Glucose Oxidation to Aggregation of Human Platelets

The effect of aggregating agents on the hexose monophosphate shunt (HMPS) and the relationship of ¹⁴CO₂ production to platelet aggregation were studied in normal volunteers. Platelets collected in ACD were suspended in modified Ringer’s bicarbonate buffer without washing and were studied before and after the addition of collagen, adenosine diphosphate (ADP), epinephrine, or thrombin. HMPS and Kreks cycle activities were estimated by the yields of ¹⁴CO₂ from glucose-1-¹⁴C (C₁) and glucose-6-¹⁴C (C₆). ¹⁴CO₂ production from each substrate was measured continuously during experiments using paired, vibrating reed electrometers and incubation flasks. Both flasks contained aliquots of the same platelet suspension. Baseline ¹⁴CO₂ production averaged 22 ± 4.5 mµmoles/hr/10⁹ platelets from C₆ as compared to 33 ± 6 mµmoles/hr/ 10⁹ platelets from C₁. Each aggregating agent gave a prompt and striking increase in ¹⁴CO₂ production from C₁. In contrast, the increase in ¹⁴CO₂ production from C₆ was not detectable for 10 min and then production increased slowly. Inhibition of ¹⁴CO₂ nate (25 mM) did not interfere with platelet aggregation. Stimulation of ¹⁴CO₂ production from C₁ by aggregating agents was unaffected by malonate. These data indicate that platelet aggregation coincides with stimulation of the HMPS, but the increase in Krebs cycle activity occurs later and is not essential for platelet aggregation.