Elevated plasma levels of apolipoprotein B (apoB) may predispose to development of premature coronary atherosclerosis. We have identified the first well localized domain of the apoB gene which can effect negative regulation of its transcription. This region binds trans-activating factors present only in apoB producing cell lines. Mutagenesis of this region causes up-regulation of its transcriptional activity. We have termed this element apoB upstream suppressor site (aBUSS) and its trans-activators the apoB repressor proteins (ARP). aBUSS and ARP may play important roles in the transcriptional modulation of apoB.

Eighteen children and young adults underwent intensive cancer therapy resulting in severe oral mucositis. Plasma and erythrocyte β-endorphin-like immunoreactivity (β-end ir) were followed serially from baseline state through the onset of painful mucositis, treatment with narcotics, and eventually resolution of the painful process. With the onset of pain and before institution of narcotic therapy, erythrocyte β-end ir showed significant reduction, with a further decrease during narcotic therapy and return toward baseline with resolution of the mucositis. Plasma β-end ir showed no significant changes. Evaluation of the erythrocyte-bound component of circulating β-end ir appears to be important when assessing changes in this endogenous opiate during pain.

Uteroglobin, a steroid-dependent, small molecular weight (15 K) protein in the rabbit, inhibited thrombin-induced aggregation of both rabbit and human gel-filtered platelets (GFP). GFP aggregation by arachidonic acid was not affected by uteroglobin. There were no effects of uteroglobin on thrombin-induced clotting of plasma or purified fibrinogen, or inhibition of thrombin by antithrombin III. Additionally, preliminary results suggest that uteroglobin does not interfere with binding of thrombin to platelets. We suggest that inhibition of platelet aggregation by uteroglobin may function in preventing thrombosis and ensuring free flow of blood through the microvasculature of the uterus and the placenta and may induce some of the antimotility effects of progesterone on the uterus.

Although progesterone is known to produce quiescence in the mammalian uterus, the mechanism of this effect is not clearly understood. Here, we report that uteroglobin, a progesterone-induced small molecular weight (16K) protein, inhibits phospholipase A2(PLA2) derived from porcine pancreas as well as from the RAW 264.7 macrophage cell line. We speculate that progesterone may exert its antimotility effects on the uterus via uteroglobin which, by inhibiting PLA2, decreases arachidonic acid release and subsequently reduces prostaglandin levels in this organ. This may explain why progesterone is so vital for the maintenance of pregnancy in almost all mammals.

Although it is widely accepted that radiolabeled prototypic delta receptor agonists label two binding sites in vitro, the mechanism by which mu ligands inhibit peptide binding as well as the identity of the binding sites remains unsettled (Rothman and Westfall, Mol. Pharmacol. 21:538–547, 1982; Bowen et al., Proc. Natl. Acad. Sci. U.S.A. 78:4818–4822, 1981). Using the site directed, receptor selective alkylating agents, BIT and FIT (Rice et al., Science 220:314–316, 1983), we describe the preparation of membranes devoid of high affinity binding sites and demonstrate that the mu agonist oxymorphone noncompetitively inhibits the binding of [3H]DADL to the residual lower affinity binding sites.

Abstract: (β‐FNA, the β ‐fumaramate methyl ester of naltrexone, has been shown to antagonize irreversibly the actions of morphine on the guinea pig ileum and mouse vas deferens bioassays but does not affect the actions of δ‐receptor ligands on the mouse vas deferens bioassay, suggesting that the compound does not irreversibly bind to the S receptor. In this paper we examine the effect of (β ‐FNA on the binding of the prototypic δ agonists, Leuenkephalin and d‐Ala2‐d‐Leu5‐enkephalin, its metabolically stable analogue, and show that treatment of membranes with β ‐FNA does lead to alterations in the in vitro properties of δ receptors.

To facilitate the quantitative study of the opiate receptor, we have developed a novel variation of the ligand binding technique. The binding of 3H-opiates to rat brain membranes is compared with the binding to slide-mounted sections of molded minced rat brain. The latter method is characterized by a high signal and a superior signal-to-noise ratio over a wide range of ligand concentrations. The results are discussed in reference to other ligand binding methodologies.

Opiate drugs alter cognitive performance and influence hippocampal excitability, including long-term potentiation (LTP) and seizure activity. The dentate gyrus (DG) contains two major opioid peptides, enkephalins and dynorphins, which have opposing effects on excitability. Enkephalins preferentially bind to delta- and mu-opioid receptors (DORs and MORs) while dynorphins preferentially bind to kappa-opioid receptors (KORs). Opioid receptors can also be activated by exogenous opiate drugs such as the MOR agonist morphine. Enkephalins are contained in the mossy fiber pathway, in the lateral perforant path (PP) and in scattered GABAergic interneurons. MORs and DORs are predominantly in distinct subpopulations of GABAergic interneurons known to inhibit granule cells, and are present at low levels within granule cells. MOR and DOR agonists increase excitability and facilitate LTP in the molecular layer. Anatomical and physiological evidence is consistent with somatodendritic and axon terminal targeting of both MORs and DORs. Dynorphins are in the granule cells, most abundantly in mossy fibers but also in dendrites. KORs have been localized to granule cell mossy fibers, supramammillary afferents to granule cells, and PP terminals. KOR agonists, including endogenous dynorphins, diminish the induction of LTP. Recent evidence indicates that opiates and opioids also modulate other processes in the hippocampal formation, including adult neurogenesis, the actions of gonadal hormones, and development of neonatal transmitter systems.