Neuropeptidomic Components Generated by Proteomic Functions in Secretory Vesicles for Cell–Cell Communication

Diverse neuropeptides participate in cell–cell communication to coordinate neuronal and endocrine regulation of physiological processes in health and disease. Neuropeptides are short peptides ranging in length from ~3 to 40 amino acid residues that are involved in biological functions of pain, stress, obesity, hypertension, mental disorders, cancer, and numerous health conditions. The unique neuropeptide sequences define their specific biological actions. Significantly, this review article discusses how the neuropeptide field is at the crest of expanding knowledge gained from mass-spectrometry-based neuropeptidomic studies, combined with proteomic analyses for understanding the biosynthesis of neuropeptidomes. The ongoing expansion in neuropeptide diversity lies in the unbiased and global mass-spectrometry-based approaches for identification and quantitation of peptides. Current mass spectrometry technology allows definition of neuropeptide amino acid sequence structures, profiling of multiple neuropeptides in normal and disease conditions, and quantitative peptide measures in biomarker applications to monitor therapeutic drug efficacies. Complementary proteomic studies of neuropeptide secretory vesicles provide valuable insight into the protein processes utilized for neuropeptide production, storage, and secretion. Furthermore, ongoing research in developing new computational tools will facilitate advancements in mass-spectrometry-based identification of small peptides. Knowledge of the entire repertoire of neuropeptides that regulate physiological systems will provide novel insight into regulatory mechanisms in health, disease, and therapeutics

Measuring Endocannabinoid Hydrolysis: Refining our Tools and Understanding

Endocannabinoids (eCBs) are lipid transmitters that are released from membrane precursors in response to specific stimuli, activate cannabinoid receptors—the molecular targets of compounds produced by Cannabis sativa—and are then rapidly inactivated by uptake and enzymatic hydrolysis. This signaling system is implicated in a wide range of biological processes, including pain sensation, immunomodulation, appetite regulation, development, and cognitive and emotional states. The balance between eCB release and inactivation determines the extent of eCB accumulation, with enzymatic hydrolysis functioning as an important limiting step. Pharmacological inhibition of eCB-hydrolyzing enzymes offers great therapeutic and experimental promise for enhancing this ubiquitous signaling system only where and when these transmitters are naturally produced. The following mini-review summarizes the latest developments concerning eCB-hydrolyzing enzymes, with an emphasis on the techniques used to measure their activities and how these have helped increase our understanding of the role that eCBs play in regulating fundamental biological functions