Maternal Nicotine Exposure During Pregnancy and Lactation: I. Effect on Glycolysis in the Lungs of the Offspring

Abstract

We investigated the effect of maternal nicotine exposure during pregnancy and lactation on carbohydrate metabolism in the neonatal lung. Female rats received nicotine (1 mg/kg body weight/day) subcutaneously from day 7 after mating. Control animals received saline. The suckling rats were killed 24 hours after the last dose of nicotine was administered to the mother on postnatal day 14. The lung tissue of 9 rat pups from 3 litters was surgically removed and the in vitro utilization of exogenous glucose (micromol/g wet lung tissue/h) was determined. Lactate production (micromol/g wet lung tissue/h) was also determined to assess glycolytic activity. Maternal nicotine exposure during pregnancy and lactation stimulated glucose turnover by 21.6% (P<.01), but suppressed glycolysis by 24.6% (P<.001) and glycogenolysis by 37.9% (P<.001). Maternal nicotine exposure during gestation and lactation had no effect on the activity of hexokinase (U/g wet lung tissue), but resulted in a lower phosphofructokinase activity (U/g wet lung tissue) in the lungs of the offspring. From the data, it appeared that the inhibition of the flux of glucose through the glycolytic pathway can be attributed to an inhibition of phosphofructokinase.

Nicotine and lung development

“…In rats, maternal nicotine exposure during pregnancy and lactation (Kordom et al, 2002) had no influence on the HK activity in the lungs of the offspring and thus the phosphorylation of glucose. Maternal nicotine exposure during pregnancy and lactation also had no effect on lactate dehydrogenase and pyruvate kinase activity in the lungs of the offspring, which means that the site of action of nicotine is between HK and lactate dehydrogenase (Maritz, 1997b).…”

“…Maternal nicotine exposure during pregnancy and lactation also had no effect on lactate dehydrogenase and pyruvate kinase activity in the lungs of the offspring, which means that the site of action of nicotine is between HK and lactate dehydrogenase (Maritz, 1997b). The decrease in the glycolytic activity, and thus the flux of glucose through this pathway, can be attributed to an inhibition of phosophofructokinase (PFK), the rate limiting enzyme of the glycolytic pathway (Kordom et al, 2002). It appears that the lower PFK activity, such as the reduced phosphorylase activity, is due to interference with PFK synthesis at either the pre or posttranslational level (Kordom, 1999), resulting in a lower concentration of PFK and thus a slower flux of glucose via glycolysis.…”

Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring

“…Maternal nicotine exposure during pregnancy and lactation also had no effect on lactate dehydrogenase and pyruvate kinase activity in the lungs of the offspring, which means that the site of action of nicotine is between hexokinase and lactate dehydrogenase [Maritz, 1997b]. The decrease in the glycolytic activity, and thus the flux of glucose through this pathway, can be attributed to an inhibition of phosophofructokinase (PFK), the rate-limiting enzyme of the glycolytic pathway [Kordom et al 2002]. It appears that the lower PFK activity, like the reduced phosphorylase activity, is due to interference with PFK synthesis at either the pre-or posttranslational level [Kordom, 1999], resulting in a lower concentration of PFK and thus a slower flux of glucose via glycolysis.…”

“…In a recent study it was shown that the activity of hexokinase is highest during the phase of rapid alveolarization in the developing lung. This implies that glycolysis is an important source of energy and of precursors to the developing lung during this phase of lung development that is characterized by rapid cell division [Kordom et al 2002]. The lower PFK activity in the lungs of the nicotine-exposed animals will therefore have an adverse impact on this phase of lung development.…”

“…In rats, maternal nicotine exposure during pregnancy and lactation [Kordom et al 2002] had no influence on the HK activity in the lungs of the offspring and thus the phosphorylation of glucose. Maternal nicotine exposure during pregnancy and lactation also had no effect on lactate dehydrogenase and pyruvate kinase activity in the lungs of the offspring, which means that the site of action of nicotine is between hexokinase and lactate dehydrogenase [Maritz, 1997b].…”