Abstract:
Previous studies have revealed a placental extract that inhibits breathing infetal sheep. In the present study of 29 chronically instrumented sheep at132±1 days of gestation, infusion of the 1-10 kDa extract inhibitedbreathing in 76% of the experiments whereas Krebs’ solutioninhibited it in 24%. It retained this activity after 6 months offreezing, after lyophilization, and upon lowering the pH during puricationfrom 8·0 to 4·0, but it inhibited breathing in only 35%when the pH was lowered to 2·0. A signicant dose-dependent effect wasobserved from a 16-fold dilution to a 4-fold concentration. Treatment of theextract with proteinase K or boiling reduced the activity to 30% or26% inhibition, respectively. The activity was not adsorbed to anion-exchange column at pH 7·0 or 8· 0, but it was at pH9· 0 and it eluted with increasing NaCl concentrations. On apolyacrylamide gel the activity was eluted at aK<emph type="8">av of 0· 66 (82%inhibition), corresponding to between 2·5 and 4·5 kDa. Thesendings suggest that a peptide produced by the placenta, with a molecular massbetween 2· 5 and 4·5 kDa, inhibits fetal breathing.