<unk> s <unk>  are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released:<unk>  A,<unk>  B, and α/β-neo-endorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of “big<unk> .” “Big<unk> ” is a 32-amino acid molecule consisting of both<unk>  A and<unk>  B.<unk>  A,<unk>  B, and big<unk>  all contain a high proportion of basic amino acid residues, in particular lysine and arginine (29.4%, 23.1%, and 31.2% basic residues, respectively), as well as many hydrophobic residues (41.2%, 30.8%, and 34.4% hydrophobic residues, respectively). Although<unk> s are found widely distributed in the CNS, they have the highest concentrations in the hypothalamus, medulla, pons, midbrain, and spinal cord.<unk> s are stored in large (80-120 nm diameter) dense-core vesicles that are considerably larger than vesicles storing neurotransmitters. These large dense-core vesicles differ from small synaptic vesicles in that a more intense and prolonged stimulus is needed to cause the large vesicles to release their contents into the synaptic cleft. Dense-core vesicle storage is characteristic of opioid peptides storage. The first clues to the functionality of<unk> s came from Goldstein et al. in their work with opioid peptides. The group discovered an endogenous opioid peptide in the porcine pituitary that proved difficult to isolate. By sequencing the first 13 amino acids of the peptide, they created a synthetic version of the peptide with a similar potency to the natural peptide. Goldstein et al. applied the synthetic peptide to the guinea ileum longitudinal muscle and found it to be an extraordinarily potent opioid peptide. The peptide was called<unk>  (from the Greek<unk> amis, meaning power) to describe its potency.<unk> s exert their effects primarily through the κ-opioid receptor (KOR), a G-protein-coupled receptor. Two subtypes of KORs have been identified: K1 and K2. Although KOR is the primary receptor for all<unk> s, the peptides do have some affinity for the μ-opioid receptor (MOR), δ-opioid receptor (DOR), and the N-methyl-D-aspartic acid (NMDA)-type glutamate receptor. Different<unk> s show different receptor selectivities and potencies at receptors. Big<unk>  and<unk>  A have the same selectivity for human KOR, but<unk>  A is more selective for KOR over MOR and DOR than is big<unk> . Big<unk>  is more potent at KORs than is<unk>  A. Both big<unk>  and<unk>  A are more potent and more selective than<unk>  B.
Dynorphin
Beta-Endorphin
Gluten exorphin
Somatostatin
Neuropil
N-Acetylserotonin
Serotonin
Endorphins