We are conducting a coordinated series of biochemical, pharmacological, physiological, and neuroanatomical studies to investigate the functional significance of dynamic peptide processing events in tachykinin and opioid neural systems. Tachykinins are small peptides with potent contractile, secretory and electrical activities. The mammalian tachykinin family includes the widely studied neuropeptide substance P and the more recently described neurokinins A and B. Mature tachykinins are derived by selective processing of preprotachykinin (PPT) molecules expressed from either of two PPT genes. To gain an in depth understanding of the dynamic molecular events underlying PPT systems, we will perform detailed analyses of mature and immature tachykinins, and PPT mRNAs. In addition, we will provide complementary analyses of endogenous opioid peptides and preproenkephalin mRNAs, in order to monitor changes at the molecular level that may accurately reflect functional interrelationships between these major neural systems. Our overall objectives are: 1) to provide biochemical descriptions and chromatographic profiles of different molecular forms of PPT-related peptides in rodent neural tissues, 2) to compare and contrast the extent of terminal amidation of tachykinin peptides in rodent neural tissues, 3) to probe the role of unamidated tachykinin precursor species in the regulation of expression of tachykinin and opioid peptides, 4) to assess the biochemical effects of hormonal, pharmacological, and physiological manipulations on interactive tachykin, opioid, and monoaminergic neural systems, 5) to probe the biochemical and molecular dynamics of interactive tachykinin and opioid systems in anatomical pathways related to pain and analgesia. Overall, the proposed studies will strengthen the molecular foundation for research on functionally interactive tachykinin- and opioid-synthesizing neural systems, and on the molecular mechanisms by which narcotics can influence sensory and affective processes.
Showing the most recent 10 out of 24 publications
