Bombesin-like peptides and receptors in normal fetal baboon lung: roles inlung growth and maturation

Previously, we have shown that bombesin-like peptide (BLP) promotes fetal l ung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP a nd BLP receptors as well as the effects of BLP an cultured normal fetal bab oon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonar y BLP, were detectable on gestational day 60 (ED60), peaked on approximatel y ED90, and then declined before term (ED180). Numbers of BLP-immunopositiv e neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, pre ceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [H -3] choline incorporation into surfactant phospholipids, electron microscop y, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cell s and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. C ell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GR P-receptor gene expression during ontogeny suggests that novel BLP receptor s and/or peptides might be implicated in these responses.