Neuropeptides enkephalin

Recent molecular cloning studies have identified aminopeptidase B as an appropriate Arg/Lys aminopeptidase (35). Molecular cloning of the bovine aminopeptidase B (AP-B) cDNA defined its primary sequence that provided production of specific antisera to demonstrate localization of AP-B in secretory vesicles that contain cathepsin L with the neuropeptides enkephalin and NPY. AP-B was also found in several neuroendocrine tissues by western blots. Recombinant bovine AP-B (35) and rat AP-B were compared. Recombinant bovine AP-B showed preference for Arg-MCA substrate compared with Lys-MCA. AP-B was inhibited by arphamenine, an inhibitor of aminopeptidases. Bovine AP-B showed similar activities for Arg-(Met)enkephalin and Lys-(Met)enkephalin neuropeptide substrates to generate (Met)enkephalin, whereas rat AP-B preferred Arg-(Met)enkephalin. Furthermore, AP-B possesses an acidic pH optimum of 5.5-6.5 that is similar to the internal pH of secretory vesicles. The significant finding of the secretory vesicle localization of AP-B with neuropeptides and cathepsin L suggests a role for this exopeptidase in the biosynthesis of neuropeptides. 

Spiny projection neurons all contain glutamic acid decarboxylase (GAD) the synthetic enzyme for the neurotransmitter GABA (Kita and Kitai 1988). In addition, most of those neurons projecting to the globus pallidus alone contain the neuropeptide enkephalin, whereas most of those which project to the substantia nigra contain the neuropeptides substance P and dynorphin (Beckstead and Kersey 1985 Gerfen and Young 1988 Haber and Watson 1983). Spiny projection neurons contain different complements of neurotransmitter receptors, and other proteins that serve to characterize particular subpopulations of striatal output neurons. These will be discussed in further detail below. 

Labeling of the neuropeptide enkephalin with functionalized tris(pyrazolyl)borate complexes Solid-phase synthesis and characterization of p-[Enk-OH]-COC6H4TpPtMe3 and p-[Enk-OH]-COC6H4TpMeRe(CO)3 On N—Nv. Me B N—N Pt—Me [HOEnk]-px y s. Me 4... 

RuCp (p-(C02H)CgH4Tp) and labelling of amino acids and the neuropeptide enkephalin. J Organomet Chem. 2009 694 862-867. 

Diabetes insipidus occurs with a loss of vasopressin production in the Brattleboro rat model 330 Mutations and knockouts of peptide-processing enzyme genes cause a myriad of physiological problems 330 Neuropeptides play key roles in appetite regulation and obesity 330 Enkephalin knockout mice reach adulthood and are healthy 331 Neuropeptides are crucial to pain perception 331... 

Suh HW, Song DK, Lee KJ, Choi SR, Kim YH. (1996). Intrathecally injected nicotine enhances the antinociception induced by morphine but not beta-endorphin, D-Pen2,5-enkephalin and U50,488H administered intrathecally in the mouse. Neuropeptides. 30(4) 373-78. 

Endorphins, dynorphins, and enkephalins are a particularly interesting group of neuropeptides. They act as endogenous opiates by producing analgetic, sedative, and euphoriant effects in extreme situations. Drugs such as morphine and heroin activate the receptors for these peptides (see p. 354). 

The occurrence of a variety of neuropeptides in the brain has been discussed in Section A. The first of these to be discovered811 was the 11-residue substance P (Table 30-4), which was isolated in 1931. Like other neuropeptides it may function either as a transmitter or neuromodulator or perhaps both. Substance P, as well as many other neuropeptides, has been localized to specific neurons. Along with somatostatin, CCK, and enkephalins, it is found in high concentrations in the basal ganglia. Enkephalin and substance P are also found in specific neural elements in the visual system of lobsters.812 In some cases a neuron contains both synaptic vesicles containing a major neurotransmitter and also vesicles containing a peptide or other cotrans-mittor. The peptide pituitary hormones ACTH, MSH, and vasopressin as well as the hypothalamic neurohormones may have effects on learning and behavior.813... 

The heterogeneity of dopaminergic neurons may also be judged by the fact that the cotransmitter systems involving dopamine and peptides are varied in the central nervous system. For example, in the corpus striatum, in addition to dopamine, acetylcholine, y-aminobutyric acid, serotonin, glutamate, and aspartate, one also finds peptides such as enkephalin, substance P, somatostatin, neuropeptide Y, cholecystokinin, neurotensin, and vasoactive intestinal peptide. Although many neuroleptics block dopamine receptors, they may have selective effects on the peptides and other parts of the brain. A few examples will be cited. 

Tu B, Timofeeva O, Jiao Y et al (2005) Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain. J Neurosci 25 1718-29 Ueda H, Fukushima N, Ge M et al (1987) Presynaptic opioid kappa-receptor and regulation of the release of Met-enkephalin in the rat brainstem. Neurosci Lett 81 309-13 van den Pol AN, Gao XB, Obrietan K et al (1998) Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 18 7962-71... 

Reduction in somatostatin and corticotrophin releasing factor immunoreactivity in cortex. No convincing evidence of change in die concentration of substance P, enkephalins, cholecystokinin, neuropeptide Y, glutamate, aspartate or GABA... 

Endorphins are small neuropeptides that are produced by the body and act to reduce pain—hence, the name endorphin (a shortened version of endogenous morphine). The term enkephalin (meaning literally in the head ) is also applied to endorphins, but usually refers to smaller molecules that have pain-relieving properties. 

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