A comparison of substance P peptide and preprotachykinin mRNA levels during development of rat medullary raphe and neostriatum.

Substance P (SP) and the mRNA coding for its precursor peptide, preprotachykinin (PPT), were measured in medullary raphe nuclei (MRN) and neostriatum (NS) over development in order to determine (1) whether PPT mRNA levels correlate with peptide development, and (2) whether changes in PPT mRNA might help to account for the apparent decline in SP seen immunohistochemically in certain brain areas postnatally. Total RNA was quantified in dissected tissue pieces using the sensitive orcinol reaction. When MRN PPT mRNA levels measured by Northern blot analysis were adjusted to total RNA levels, PPT mRNA per MRN increased over development with a profile similar to that seen for SP peptide. Moreover, both peptide and mRNA levels exhibited a similar decline after postnatal day 15. Therefore, developmental regulation of SP biosynthesis in the MRN may, in part, explain previous evidence documenting a postnatal decline in SP there. In the NS, SP peptide and PPT mRNA increased with a similar profile from E18 through the first postnatal week. Thereafter, SP increased less rapidly than its mRNA, indicating incongruities in prohormone message and processed peptide in the NS.