Distinct functions of the two isoforms of dopamine D2 receptors

Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions in vivo; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.     

Mechanism of human immunodeficiency virus type I entry into the target cells

Based on the recent advances of the research on the mechanism of HIV-1 infection, a novel model to elucidate the mechanism of HIV entry into the target cells is proposed and the perspective about the putative receptor is discussed in this review. Understanding of the crystal structure of HIV-1 transmembrane protein gp41 and the functions of HIV-1 receptor, co-receptor and the putative receptor will lead to developing effective HIV vaccine and anti-HIV drugs.     

Growth control of activated, synchronized murine B cells by the C3d fragment of human complement

Three restriction points control the cell cycle of activated B lymphocytes. The first occurs directly after mitosis and is controlled by the occupancy of surface-bound immunoglobulin. The second is observed approximately 4 h after mitosis in the G1 phase of the cycle, that is, before DNA replication, and is controlled by growth factors that are produced by macrophages which we have previously classified as alpha-type factors. The third restriction point occurs in the G2 phase, 2-4 h before mitosis, and is controlled by beta-type growth factors probably produced by helper T lymphocytes. The third component of complement, C3, has long been implicated in the control of B-cell responses. C3 is secreted by monocytes and macrophages. We have found recently that crosslinked, but not soluble, human C3 stimulates activated, but not resting, murine B cells to thymidine uptake. Here we investigate the role of C3b and C3d in the progression of the cell cycle of activated, synchronized murine B cells. We find that crosslinked C3d replaces the action of alpha-factors within the cell cycle of these cells and allows entry into S phase. In contrast, soluble C3d inhibits the action of alpha-factors. This implies that a C3d-specific receptor, probably the murine analogue to the human complement receptor CR2, is a growth factor receptor on activated B cells that will give the cell a growth-positive signal when it is crosslinked, while occupancy by the soluble form of C3d will result in inhibition of the action of alpha-factors or of crosslinked C3b or C3d. A stretch of weak homology between the cDNA sequence of murine C3d and those of murine growth factors indicates that an insulin-like growth factor could be the active principle of C3d that controls the cell cycle of activated B cells.     

Flow Cytometry Analysis of Human Interferon α/β-receptor Expresion on H9,Raji and U937 Cells

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Mechanism of hmnan immunodeficiency virus type I entry into the target cells

Based on the recent advances of the research on the mechanism of HIV-1 infection, a novel model to elucidate the mechanism of HIV entry into the target cells is proposed and the perspective about the putative receptor is discussed in this review. Understanding of the crystal structure of HIV-1 transmembrane protein gp41 and the functions of HIV-1 receptor, co-receptor and the putative receptor will lead to developing effective HIV vaccine and anti-HIVdrugs.     

Nicotinamide desamidase in the culture medium of neuroblastoma cells]

Important amounts of nicotinic acid appear in the growth medium of neuroblastoma cell cultures. It is shown that an enzyme released by the cells into the growth medium deamidates the nicotinamide supplied by the growth medium to nicotinic acid.     

Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses

The role of the opioid system in controlling pain, reward and addiction is well established, but its role in regulating other emotional responses is poorly documented in pharmacology. The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids. We have generated Oprd1-deficient mice and compared the behavioural responses of mice lacking Oprd1, Oprm (ref. 6) and Oprk1 (ref. 7) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1-/- mutants, suggesting that kappa-receptors do not have a role in this aspect of opioid function; opposing phenotypes in Oprm-/- and Oprd1-/- mutants which contrasts with the classical notion of similar activities of mu- and delta-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1-/- mice, indicating that delta-receptor activity contributes to improvement of mood states. We conclude that the Oprd1-encoded receptor, which has been proposed to be a promising target for the clinical management of pain, should also be considered in the treatment of drug addiction and other mood-related disorders.     

Biological function of H1V-1 transmembrane protein gp41

Since 1992, the study of biological functions of HIV-1 gp41 has made great progress. Experimental evidence from several research groups demonstrated that gp41 has a putative cellular receptor. A recombinant soluble gp41 (aa539–684) and gp41 immunosuppressive peptide (aa583–599) could bind to human B lymphocytes and monocytes, but weakly bind to T lymphocytes. It was found that gp41 contains two cellular binding sites (aa583–599 and 641–675). GP41 could selectively inhibit cell proliferation of human T, B lymphocytes and monocytes, enhance human MHC class I, II and ICAM-1 molecule expression on cell surface. Gp41 binding proteins and a monoclonal antibody against the first binding site could inhibit this modulation effect. Amino acid sequence homology exists between gp41 and human type I interferons, and the homologous region is located in the first binding site on gp41 and in the receptor binding site on type I interferons. Studies in other groups indicate that both binding sites in gp41 may be associated with HIV infection of cells. Peptides containing two binding sites could respectively inhibit HIV infection of cells. A monoclonal antibody recognizing the second binding site could neutralize lab-strains and recently separated strains of HIV-1. Besides, antibodies against two regions (homologous with gp41 binding sites) of SIV transmembrane protein gp32 could protect macaques from SIV infection. These results suggest that the study of gp41 binding sites and cellular receptor could contribute to understanding the mechanism of HIV infection and to developing HIV vaccine and anti-HIV drugs.