We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 ؎ 114 pg͞mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the eff luent of isolated, perfused rat heart (34.5 ؎ 4.7 pg͞min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription-PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart's chambers suggests an autocrine and͞or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and͞or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.Vasopressin and oxytocin (OT) are synthesized predominantly in the magnocellular neurons of the supraoptic nucleus and paraventricular nucleus as well as in the parvocellular neurons within the paraventricular nucleus as parts of larger precursor molecules (1). The precursors are modified posttranslationally and are transported to the posterior pituitary, where the final bioactive peptide products are stored until they are released into the blood stream. Despite being the first peptide hormone to be characterized and synthesized, the effects of oxytocin long were considered to be restricted to stimulation of uterine contractions during labor and milk ejection during lactation. However, OT is found in equivalent concentrations in the neurohypophysis and plasma of both sexes, which suggests that it also may have other physiological roles (2). Moreover, in the central nervous system, OT-containing axons terminate in several brain stem nuclei known to be involved in cardiovascular control, suggesting a potential role for OT in central cardiovascular regulation (3, 4). Indeed, decreased blood pressure may be observed in response to oxytocin given intracerebroventricularly (5), and the inhibition of brain OT synthesis by an antisense oligonucleotide increased blood pressure in rats (6). In primates or humans, the administration of oxytocin often is associated with a decrease in blood pressure (7,8). Peripherally injected OT decreases mean arterial pressure in rats by unknown mec...

BackgroundHIV proteins Nef and Vpu down-modulate various host factors to evade immune defenses. Indeed, the CD4 receptor is down-regulated by Nef and Vpu, whereas virion-tethering BST2 is depleted by Vpu. Antibody-dependent cell-mediated cytotoxicity (ADCC) is increasingly recognized as a potentially powerful anti-HIV response. Given that epitopes which are specific for ADCC-competent anti-HIV antibodies are transitionally exposed upon CD4-mediated HIV entry, we investigated whether by depleting CD4 and BST2, HIV could negatively affect ADCC function.ResultsUsing anti-envelope (Env) Abs A32 and 2G12 to trigger ADCC activity, we find that interactions between CD4 and Env within infected cells expose ADCC-targeted epitopes on cell-surface Env molecules, marking infected T cells for lysis by immune cells. We also provide evidence to show that by cross-linking nascent virions at the plasma membrane, hence increasing cell-surface Env density, BST2 further enhances the efficiency of this antiviral process. The heightened susceptibility of T cells infected with a virus lacking Nef and Vpu to ADCC was recapitulated when plasmas from HIV-infected patients were used as an alternative source of Abs.ConclusionsOur data unveil a mechanism by which HIV Nef and Vpu function synergistically to protect infected cells from ADCC and promote viral persistence. These findings also renew the potential practical relevance of ADCC function in vivo.