Adv Exp Med Biol
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Opioids such as morphine are potent analgesic and addictive compounds. Chronic morphine use also induces immunomodulatory and immunosuppressive effects, as especially evident in HIV-infected patients. Morphine acts on the immune cells primarily through its binding to mu-opioid receptors on the plasma membrane. ⋯ The results of the competitive RT/PCR indicated that CEM x174 cells expressed KOR mRNA constitutively, in the order of femto-grams. Treatment of 10 microM of morphine resulted in the up-regulation of KOR gene expression 24 hr post-treatment. The observed morphine effect could be reversed by treating the cells with either naloxone (a KOR-partially selective antagonist) or nor-Binaltorphimine (a KOR-selective antagonist).
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Small, muscular pulmonary arteries (PAs) constrict within seconds of the onset of alveolar hypoxia, diverting blood flow to better-ventilated lobes, thereby matching ventilation to perfusion and optimizing systemic PO2. This hypoxic pulmonary vasoconstriction (HPV) is enhanced by endothelial derived vasoconstrictors, such as endothelin, and inhibited by endothelial derived nitric oxide. However, the essence of the response is intrinsic to PA smooth muscle cells in resistance arteries (PASMCs). ⋯ However, inhibition of complex 1 of the mitochondrial electron transport chain mimics hypoxia in that it inhibits IK, reduces the production of activated O2 species and causes vasoconstriction. We hypothesize that a redox O2 sensor, perhaps in the mitochondrion, senses O2 through changes in the accumulation of freely diffusible electron donors. Changes in the ratio of reduced/oxidized redox couples, such as NADH/NAD+ and glutathione (GSH/GSSG) can reduce or oxidize the K+ channels, resulting in alterations of PA tone.
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Prolactin (PRL), synthesized by the anterior pituitary and to a lesser extent by numerous extrapituitary tissues, affects more physiological processes than all other pituitary hormones combined. This hormone is involved in > 300 separate effects in various vertebrate species where its role has been well documented. The initial step in its action is the binding to a specific membrane receptor which belongs to the superfamily of class 1 cytokine receptors. ⋯ PRL-binding sites have been identified in a number of cells and tissues of adult animals. Disruption of the gene for the PRL receptor has provided a new animal model with which to better understand the actions of PRL on mammary morphogenesis and mammary gland gene expression. The recent availability of genetic mouse models provides new insights into mammary developmental biology and how the action of a hormone at specific stages of development can have effects later in life on processes such as mammary development and breast cancer initiation and progression.