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Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce inflammatory cytokines and chemokines. The expressed chemokines are thought to be involved in the migration of inflammatory cells into the synovium. In this study we show that CCL2/monocyte chemotactic protein-1, CCL5/RANTES, and CXCL12/stromal cell-derived factor-1(More)
We obtained a primary culture of prostatic cells by an explant method from patients with benign prostatic hypertrophy (BPH). Ultrastructural morphology and growth characteristics of these cells conformed to those reported for smooth muscle cells isolated from vascular and visceral tissue sources. The cells retained their original character including the(More)
The effects of endothelins on human prostatic smooth-muscle cell growth were examined. Endothelin-1 and endothelin-3 induced a concentration-dependent increase in DNA synthesis and also promoted cell growth. Use of subtype selective antagonists BQ-123 ((cyclo(D-Trp-D-Asp(ONa)-Pro-D-Val-Leu); endothelin ET(A) receptor selective) and BQ-788(More)
The chemokine receptor CCR5 is an attractive target for HIV-1 drug development, as individuals whose cells lack surface CCR5 expression are highly resistant to HIV-1 infection. CCR5 ligands, such as CCL5/RANTES, effectively inhibit HIV-1 infection by competing for binding opportunities to the CCR5 and inducing its internalization. However, the inherent(More)
The species selectivity of receptor antagonists often hinders their preclinical assessment in vivo. In order to evaluate human selective CC chemokine receptor type 5 (CCR5) antagonists in vivo, we generated human CCR5 transgenic mice that expressed the transgene on both peripheral blood leukocytes as well as thymocytes. The selective CCR5 ligand CC(More)
We investigated the antagonistic activity of (R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl) urea (YM022), a benzodiazepine derivative, at CCKB/gastrin receptors. This compound potently inhibited [125I]CCK-8 binding to rat brain CCKB/gastrin receptors with a Ki value of 0.26 nM, but it showed weak(More)
We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM.(More)
1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC(More)
The species selectivity of four structurally different compounds, SCH-351125, E-913, TAK-779 and UK-427857 has been examined using cloned human, rhesus, and mouse CCR5 receptors. SCH-351125 and E-913 potently inhibited the binding of [125I]-CCL3 to human CCR5, but their inhibitory activities against rhesus CCR5 were more than 10-fold weaker. In contrast,(More)
1. Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell). 2. [125I]-ET-1 and [125I]-ET-3 binding studies revealed that both ETA and ETB receptors were present in the HP cells, and the ratio of ETA to ETB receptors was 1.4:1. 3. Analysis of ET(More)