Role of calmodulin as an endogenous initiatory factor in compensatory lung growth after pneumonectomy

Compensatory lung growth after pneumonectomy is a well established phenomenon in young humans and experimental animals. To date, the cellular initiating and/or regulatory factor(s) responsible for this growth response have yet to be established. We have studied changes in lung content and activity of calmodulin, a calcium-dependent regulatory protein in relation with lung mass and DNA content during postpneumonectomy compensatory lung growth in 4-week-old rats. We observed that after left pneumonectomy, right lung calmodulin content (measured by radioimmunoassay) and calmodulin activity (measured by cyclic nucleotide phosphodiesterase activation) were increased at days 1 and 2 after surgery in the pneumonectomized rats, preceding the increase of lung mass and DNA content which started at day 3. Treatment of the pneumonectomized rats with a highly specific calmodulin antagonist, trifluoperazine, immediately after the surgery, resulted in diminished lung calmodulin activity, sparing the calmodulin content, and in concomitant reduction of lung mass and DNA content to values intermediate between those of controls and the pneumonectomized animals. Based on these findings, we conclude that calmodulin may be an important intracellular (possibly, autocrine) initiatory or facilitatory factor in compensatory hyperplastic lung growth after pneumonectomy.