Substance P and central respiratory activity: a comparative in vitro studyon foetal and newborn rat

Experiments were performed in vitro on foetal (embryonic days 18 to 21, E18 -21) and newborn rat (postnatal days 0 to 3, P0-3) brainstem spinal cord pr eparations to analyse the perinatal developmental changes in the effects in duced by substance P. Superfusion of the preparations with SP-containing ar tificial cerebrospinal fluid (aCSF) induced significant increase in the res piratory frequency of newborn rats (10(-9) M), whereas concentration up to 10(-7) M induced no change in foetal preparations. A whole cell patch clamp approach was used to record intracellularly from phrenic motoneurones. In newborn or E20-21 foetal rats SP-containing aCSF depolarised the phrenic mo toneurones, increased their input resistance, reduced the rheobase current and shifted the frequency-intensity curves upward. In E18 foetal rats, no c hange was evoked by SP. A peptidase inhibitor mixture was used to block the enzymatic degradation of endogenous SP. This mixture was ineffective in ch anging the respiratory frequency in newborn and foetal preparations. In new born rat phrenic motoneurones, the peptidase inhibitor mixture induced chan ges similar to those caused by SP but no change was induced in foetal rats. These results indicate that SP may modulate (i) the activity of the respir atory rhythm generator in newborn but not in foetal rats, and (ii) the acti vity of phrenic motoneurones at E20, E21 and in newborn rats but not at E18 . Results obtained using the peptidase inhibitor mixture suggest that endog enous SP is probably not involved in the control of the respiratory rhythm in the prenatal period, but may influence the activity of the phrenic moton eurones after birth. (C) 1999 Elsevier Science B.V. All rights reserved.