Characterizing intercellular signaling peptides in drug addiction

Abstract

Intercellular signaling peptides (SPs) coordinate the activity of cells and influence organism behavior. SPs, a chemically and structurally diverse group of compounds responsible for transferring information between neurons, are broadly involved in neural plasticity, learning and memory, as well as in drug addiction phenomena. Historically, SP discovery and characterization has tracked advances in measurement capabilities. Today, a suite of analytical technologies is available to investigate individual SPs, as well as entire intercellular signaling complements, in samples ranging from individual cells to entire organisms. Immunochemistry and in situ hybridization are commonly used for following preselected SPs. Discovery-type investigations targeting the transcriptome and proteome are accomplished using high-throughput characterization technologies such as microarrays and mass spectrometry. By integrating directed approaches with discovery approaches, multiplatform studies fill critical gaps in our knowledge of drug-induced alterations in intercellular signaling. Throughout the past 35 years, the National Institute on Drug Abuse has made significant resources available to scientists that study the mechanisms of drug addiction. The roles of SPs in the addiction process are highlighted, as are the analytical approaches used to detect and characterize them.

Mass Spectrometry Screening Reveals Peptides Modulated Differentially in the Medial Prefrontal Cortex of Rats with Disparate Initial Sensitivity to Cocaine

“…The neurochemical effects of drugs of abuse have traditionally been studied by focused monitoring of changes in a particular peptide, precursor protein, or mRNA, targeted by selective probes such as antibodies or oligonucleotides (49). We take an alternate route and explore global changes in peptide levels in anatomically defined brain regions to find those that may serve as markers of brain response to acute stimulation with cocaine.…”

MALDI Mass Spectrometric Imaging Using the Stretched Sample Method to Reveal Neuropeptide Distributions in Aplysia Nervous Tissue

“…Tissue stretching and profiling has been demonstrated on mammalian spine and other tissues, , and so, the imaging protocols are suitable for a variety of tissue types besides the Aplysia ganglia used here. Stretched imaging has applications in MS imaging of morphologically and chemically heterogeneous structures in the nervous system where changes in neuropeptide expression and transport caused by activity dependent changes, drugs of abuse, or progressive disease states can be spatially localized. Another exciting application complements peptidomics studies from newly characterized animal models after a number of new prohormones are discovered; − the stretched sample imaging method can be used in a global fashion to determine peptide distributions without the need to develop specific antibodies for literally dozens of new prohormones and hundreds of new neuropeptides.…”

d-Alanine in the islets of Langerhans of rat pancreas

“…The quality of islet isolation was determined by visual examination of the collected islets and direct matrix-assisted laser/desorption ionization-mass spectrometry profiling of their peptide content (Fig. S1B) [36,37]. After additional washes with the Krebs-Ringer solution, 7–20 islets were placed into individual plastic Protein LoBind tubes (Eppendorf, Hauppauge, NY) filled with 0.4 mL of Krebs-Ringer solution and incubated for 30 min at 37 °C bubbled with a 95% O 2 and 5% CO 2 gas mixture.…”