Enkephalin modulators

Kalivas, Peter W., Patricia Duffy, Roger Dilts, and Raymond Abhold. 1988. "Enkephalin Modulation of A10 Dopamine Neurons A Role in Dopamine Sensitization." Annals of the New York Academy of Sciences 537 405-14. 

Marotd T, Haberstok H, Sverko V, Hi sak I (1992) Met- and Leu-enkephalin modulate superoxide anion release from human polymorphonuclear cells. Ann N Y Acad Sci 650 146—153. 

Figure 15.9 Peptide modulation of striatal input to the globus pollidus. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. 15.2 for details) is thought to inhibit GABA release from the same terminals so that feedback (auto) inhibition is reduced. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. (See Henry and Brotchie 1996 and Maneuf et al. 1995)...

The body modulates pain through several processes. The endogenous opiate system consists of neurotransmitters (e.g., enkephalins, dynorphins, and /1-endorphins) and receptors (e.g., fl, S, k) that are found throughout the CNS. Endogenous opioids bind to opioid receptors and modulate the transmission of pain impulses. 

The mobility of tyrosine in Leu3 enkephalin was examined by Lakowicz and Maliwal/17 ) who used oxygen quenching to measure lifetime-resolved steady-state anisotropies of a series of tyrosine-containing peptides. They measured a phase lifetime of 1.4 ns (30-MHz modulation frequency) without quenching, and they obtained apparent rotational correlation times of 0.18 ns and 0.33 ns, for Tyr1 and the peptide. Their data analysis assumed a simple model in which the decays of the anisotropy due to the overall motion of the peptide and the independent motion of the aromatic residue are single exponentials and these motions are independent of each other. 

Impulse traffic in the neo- and pa-leospinothalamic pathways is subject to modulation by descending projections that originate from the reticular formation and terminate at second-order neurons, at their synapses with first-order neurons, or at spinal segmental interneurons (descending antinociceptive system). This system can inhibit impulse transmission from first- to second-order neurons via release of opio-peptides (enkephalins) or monoamines (norepinephrine, serotonin). 

The most potent and pervasive pain suppression system appears to be provided by endogenous opioids, particularly methionine encephalin and beta endorphin. These opioids and their receptors are widely distributed at several levels in the central nervous system (Mansour et al., 1988). Enkephalins appear to control the responses of dorsal horn neurons and may also modulate pain... 

Modulation of Ganglioside Synthesis by Enkephalins, Opiates, and Prostaglandins... 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

J(delta) Supraspinal and spinal analgesia modulation of hormone and neurotransmitter release Enkephalins > > endorphins and dynorphins... 

Taube HD, Borowski E, Endo T et al (1976) Enkephalin a potential modulator of noradrenaline release in rat brain. Eur J Pharmacol 38 377-80... 

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... 

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