The Experts below are selected from a list of 348 Experts worldwide ranked by ideXlab platform
James H. Meador-woodruff - One of the best experts on this subject based on the ideXlab platform.
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Prodynorphin-derived Peptide Expression in Primate Cortex and Striatum
Neuropeptides, 1994Co-Authors: Daniel J. Healy, James H. Meador-woodruffAbstract:Abstract The distributions of four prodynorphin-derived peptides, dynorphin A (1–17), dynorphin A (1–8), dynorphin B, and α-neo-endorphin were determined in 10 cortical regions and the striatum of the old world monkey (Macaca nemestrina). α-neo-endorphin was the most abundant peptide in both cortex and striatum. The concentrations of all four peptides were significantly greater in the striatum compared to the cortex. In general, concentrations of each peptide tended to be higher in allocortex than in neocortex. Possible inter- and intradomain processing differences, as estimated by ratios of these peptides, did not vary within cortex, but the intradomain peptide ratio, dyn A (1–17)/dyn A (1–8), was significantly greater in cortex than in striatum. These results indicate that prodynorphin is, in some ways, uniquely processed in the primate. Particularly unusual is the relatively low abundance of prodynorphin-derived products in the cortex, in the face of moderately high levels of Kappa Opiate Receptor expression.
Daniel J. Healy - One of the best experts on this subject based on the ideXlab platform.
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Prodynorphin-derived Peptide Expression in Primate Cortex and Striatum
Neuropeptides, 1994Co-Authors: Daniel J. Healy, James H. Meador-woodruffAbstract:Abstract The distributions of four prodynorphin-derived peptides, dynorphin A (1–17), dynorphin A (1–8), dynorphin B, and α-neo-endorphin were determined in 10 cortical regions and the striatum of the old world monkey (Macaca nemestrina). α-neo-endorphin was the most abundant peptide in both cortex and striatum. The concentrations of all four peptides were significantly greater in the striatum compared to the cortex. In general, concentrations of each peptide tended to be higher in allocortex than in neocortex. Possible inter- and intradomain processing differences, as estimated by ratios of these peptides, did not vary within cortex, but the intradomain peptide ratio, dyn A (1–17)/dyn A (1–8), was significantly greater in cortex than in striatum. These results indicate that prodynorphin is, in some ways, uniquely processed in the primate. Particularly unusual is the relatively low abundance of prodynorphin-derived products in the cortex, in the face of moderately high levels of Kappa Opiate Receptor expression.
Jia Bei Wang - One of the best experts on this subject based on the ideXlab platform.
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Human Kappa Opiate Receptor second extracellular loop elevates dynorphin's affinity for human mu/Kappa chimeras.
Journal of Biological Chemistry, 1994Co-Authors: Jia Bei Wang, Peter S. Johnson, Jun Min Wu, Wen Fei WangAbstract:Abstract To investigate roles of second extracellular loop sequences in peptide and nonpeptide ligand recognition by human Opiate Receptors, we have constructed a chimeric Receptor in which this domain of the human mu Opiate Receptor has been replaced with that of the human Kappa Opiate Receptor. The chimeric Opiate Receptor displays dramatically increased affinity for dynorphin peptides. Affinities for dynorphin A-(1-17), dynorphin A-(1-13), and alpha-neoendorphin increase by up to 250-fold when compared with the wild-type human mu Opiate Receptor. The chimera maintains recognition of the mu-selective ligands morphine and [D-Ala2,MePhe4,Gly-ol5]enkephalin and displays no significant changes in affinity for the Kappa-selective small molecule ligand U50,488. The chimeric Opiate Receptor displays evidence for effective G-protein coupling; 100 nM dynorphin A-(1-17) is as effective as 100 nM morphine at inhibiting forskolin-stimulated adenyl cyclase activity through actions at the chimeric Receptor. These data suggest that the putative second extracellular loop contributes substantially to the Kappa Receptor's selectivity in dynorphin ligand recognition.
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mu Opiate Receptor: cDNA cloning and expression
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Jia Bei Wang, Y. Imai, C. M. Eppler, P. Gregor, C. E. Spivak, George R UhlAbstract:Abstract mu Opiate Receptors recognize morphine with high affinity. A 2.1-kb rat brain cDNA whose predicted translation product displays 63% identity with recently described delta and Kappa Opiate Receptor sequences was identified through polymerase chain reaction and cDNA homology approaches. This cDNA recognizes a 10.5-kb mRNA that is expressed in thalamic neurons. COS-cell expression confers naloxonazine-, Na(+)-, and GTP-sensitive binding of mu but not delta or Kappa opioid ligands. Expressing cells bind morphine, [D-Ala2,N-methyl-Phe4,glyol5]enkephalin (DAMGO), and [D-Ala2,D-Leu5]enkephalin (DADLE) with nanomolar or subnanomolar affinities, defining a mu Opiate Receptor that avidly recognizes analgesic and euphoric Opiate drugs and opioid peptides.
Laszlo Hackler - One of the best experts on this subject based on the ideXlab platform.
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mu delta and Kappa Opiate Receptor binding of tyr mif 1 and of tyr w mif 1 its active fragments and two potent analogs
Life Sciences, 1994Co-Authors: James E Zadina, Abba J Kastin, Laszlo HacklerAbstract:The relative binding to mu, delta, and Kappa Opiate Receptors was characterized for the brain peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), and two fragments of Tyr-W-MIF-1 (Tyr-Pro-Trp and Tyr-Pro-Trp-Gly) previously shown to have antagonist as well as agonist activity in the guinea pig ileum. Tyr-MIF-1 had relatively low affinity (Ki = 1 microM at the mu site) but high selectivity (400- and 700-fold greater affinity for mu over delta and mu over Kappa binding). Tyr-W-MIF-1 (Ki = 71 nM at the mu site) showed higher affinity binding to all three sites than Tyr-MIF-1 while retaining 200-fold selectivity for mu over delta and Kappa Receptors. The affinity of the fragments of Tyr-W-MIF-1 was lower for mu but higher for delta Receptors. We also tested two cyclized analogs of Tyr-W-MIF-1 that were about 200-fold more active than the parent compound in producing analgesia. These analogs showed higher affinity binding to all three Opiate Receptors. One of the analogs showed binding affinity to mu sites (Ki = 1.3 nM) that was within 3-fold of that of the potent analog of enkephalin, DAMGO. Thus, brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous Opiates, can provide high selectivity for mu Opiate Receptors. Analogs based on one of them, Tyr-Pro-Trp-Gly-NH2, show high affinity as well as potent analgesic activity.
Hemendra N Bhargava - One of the best experts on this subject based on the ideXlab platform.
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abstinence from u 50 488h a Kappa Opiate Receptor agonist decreases the binding of 3h dapt to 5 ht1a Receptors in the hypothalamus of the rat
Neuropharmacology, 1992Co-Authors: Veeranna P L Reddy, Hemendra N BhargavaAbstract:Abstract The effect of trans -( ± )-3,4-dichloro- N -methyl- N -[2-(1-pyrrolidinyl) cyclohexyl]-benzene-acetamide methane sulfonate (U-50,488H), a κ-Opiate agonist-induced tolerance and abstinence on 5-HT 1A Receptors was determined in regions of the brain and spinal cord of the rat. The administration of U-50,488H (25 mg/kg, i.p., twice daily) to male Sprague-Dawley rats for 4 days resulted in the development of almost complete tolerance to its analgesic and hypothermic effects. On day 5, the animals were divided into tolerant and abstinent groups and sacrificed. The brain and spinal cord were excised from all groups of rats and the brain was dissected into 6 regions, namely, amygdala, hypothalamus, striatum, midbrain, pons + medulla and cortex. The 5-HT 1A Receptors were characterized by using [ 3 H]8-hydroxy-2-(di- n -propylamino)tetralin ([ 3 H]DPAT) as the ligand. The binding constants ( B max and K d values) of [ 3 H]DPAT in regions of the brain and spinal cord of rats tolerant to U-50,488H and vehicle did not differ. However, the B max value of [ 3 H]DPAT in the hypothalamus of U-50,488H-abstinent rats was decreased but the K d value did not change. In the other regions of the brain and spinal cord of U-50,488H-abstinent rats, the B max and K d values of [ 3 H]DPAT were unaffected. Subcutaneous administration of DPAT produced hypothermic response in vehicle- and U-50,488H-treated rats. The intensity of this effect was more marked in U-50,488H-abstinent group. It is concluded that 5-HT 1A Receptors are down-regulated in the hypothalamus of U-50,488H-abstinent rats but the hypothermic response to 5-HT 1A agonist is intensified.
