Dopamine receptor modulating peptide

The dopamine receptor modulating peptide Pro-Leu-Gly-NH2 (PLG) selectively enhances the binding of agonists to dopamine receptors in the mammalian central nervous system. Johnson and co-workers at the University of Minnesota and McMaster University have prepared bicyclic 5,5- and 6,5-thiazolidine lactam peptidomimetics (82, 83) in an attempt to elucidate the bioactive conformations of PLG. 

Since cholecystokinin peptides show a neuroleptic-like profile in several screening tests for neuroleptics, cholecystokinin-dopamine interactions are of interest, especially the modulation of cholecystokinin release by dopamine receptors (Table 1). In the rat striatum both Di and D2 receptor activation was reported to increase, and both Di and D2 receptor blockade to depress, the release of the peptide. 

Macrophages/DCs and lymphocytes express a variety of adrenergic receptors. Increased concenh ations of NE or dopamine can modulate T cells polarization toward Th2 profile, stimulate IL-4, IL-5, and IL-13 secretion (Kohm and Sanders, 2001). The same Th2 polarization can be induced by histamine, serotonin, neuropeptides such as substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, a-melanocyte-stimulating hormone, and leptin (Steinman, 2004). 

It has been suggested that modafinil increases wakefulness by activating ai noradrenergic receptors or hypothalamic cells that contain the peptide hypocre-tin [3], or that it may act by modulating the GABAergic tone that might lead to an increased dopamine release in the nucleus accumbens. On the other hand, modafinil does not have any effect in DAT knockout mice. 

Opioid binding at medullary sites is consistent with the respiratory depressant effects of the drugs. Binding in the nucleus accumbens and the resultant release of dopamine by the /x- and 8-opioids is linked to the development of physical dependence. However, the K-opioids, which also bind extensively in the nucleus accumbens, are linked to a decrease in dopamine release, possibly explaining their lower abuse liability. The localization of different receptor subtypes within different-size fiber pathways has been established. The x- and 8-receptors appear associated with the large-diameter fibers, while the K-receptors appear to be located in the small to medium-size fiber bundles of the dorsal root ganglia. Such differences may explain the modulation of specific types of nociceptive stimuli by the different opioid agonists and opioid peptides. 

The type of response normally elicited by glutamate, GABA, ACh, dopamine, norepinephrine, serotonin (5HT), and the opioid peptides and the modulations induced by drugs affecting the receptors relevant to each of these transmitters is succinctly presented. 

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