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McAtee LC Sutton SW Rudolph DA Li X Aluisio LE Phuong VK Dvorak CA Lovenberg TW Carruthers NI Jones TK 《Bioorganic & medicinal chemistry letters》2004,14(16):4225-4229
Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX(1)R and OX(2)R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX(2)R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5S)-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea, which is bound by the OX(2)R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX(2)R over the OX(1)R. 相似文献
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Miller NE Michel CC Nanjee MN Olszewski WL Miller IP Hazell M Olivecrona G Sutton P Humphreys SM Frayn KN 《American journal of physiology. Endocrinology and metabolism》2011,301(4):E659-E667
Peptides secreted by adipose tissue (adipokines) may enter blood via capillaries or lymph. The relative importance of these pathways for a given adipokine might influence its biological effects. Because this has not been studied in any species, we measured the concentrations of seven adipokines and eight nonsecreted proteins in afferent peripheral lymph and venous plasma from 12 healthy men. Data for nonsecreted proteins were used to derive indices of microvascular permeability, which in conjunction with the molecular radii of the adipokines were used to estimate the amounts leaving the tissue via capillaries. Transport rates via lymph were estimated from the lymph adipokine concentrations and lymph flow rates and total transport (secretion) as the sum of this and capillary transport. Concentrations of nonsecreted proteins were always lower in lymph than in plasma. With the exception of adiponectin, adipokine concentrations were always higher in lymph (P < 0.01). Leptin and MCP-1 were secreted at the highest rates (means: 43 μg/h or 2.7 nmol/h and 32 μg/h or 2.4 nmol/h, respectively). IL-6 and MCP-1 secretion rates varied greatly between subjects. The proportion of an adipokine transported via lymph was directly related to its molecular radius (r(s) = +0.94, P = 0.025, n = 6), increasing from 14 to 100% as the radius increased from 1.18 (IL-8) to 3.24 nm (TNFα). We conclude that the lymph/capillary partitioning of adipokines is a function of molecular size, which may affect both their regional and systemic effects in vivo. This finding may have implications for the physiology of peptides secreted by other tissues. 相似文献
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G. Albin Matson H. Eldon Sutton B. Etcheverry Raul Jane Swanson Abner Robinson 《American journal of physical anthropology》1967,27(2):157-193
This is the fourth paper in a series on the distribution of blood groups among Indians of South America. It reports the findings on the Indians of Chile and the Polynesians of Chile's Easter Island. Blood specimens were procured from the following putatively pure Indians and unmixed Polynesians: 44 Alacaluf of Puerto Eden, Isla Wellington, 141 Mapuche (Araucanian) of Lonquimay, Malleco Province, 80 Atacameños of Antofagasta Province, and 45 Polynesians of Easter Island. These 310 samples were tested for blood factors in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, K-k, Lewis, Duffy, Kidd and Diego systems, and for the Wright (Wra) agglutinogen. Serum samples were tested for haptoglobins and transferrins. Hemolysates prepared from the blood clots were tested for hemoglobin types. The results are presented as phenotype incidences and calculated gene frequencies in appropriate tables. Locations of the populations from which blood samples were procured are shown on two maps. The high frequencies for the O gene usually reported for South American Indians obtain in putatively pure Chilean Indians but A1 is high in Easter Island Polynesians. In both Indians and Polynesians M, s, R1 (CDe), R2 (cDE), Lub, k, LeH, and Fya gene frequencies are high and B, N, S, Mia, Vw, Rº (cDe), r (cde), Lua, K, Le1, Fyb, and Wra (Ca) are low or absent. The Diego (Di) gene is present in the Mapuche and Atacameños but absent in the Alacaluf and Polynesians. Hp1 gene frequencies were determined only in the Alacaluf and Atacameños, in which they are 0.48 and 0.67 respectively. Transferrins were determined for the Alacaluf and Atacameños Indians and all were classified as Tf C. All Chilean Indian and Polynesian specimens were tested electrophoretically for hemoglobin types and all contained only hemoglobin (A) as a major component. 相似文献