Characterization of Postjunctional Alpha-i and Alpha -2 Adrenoceptors Activated by Exogenous or Nerve-Released Norepinephrine in the Canine Saphenous Vein

Experiments were designed to characterize alpha-i and alpha-2 adrenoceptor-mediated effects in the canine saphenou

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

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Latency Associated Peptide Has In Vitro and In Vivo Immune Effects Independent of TGF-β1

Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex. Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work shows that LAP can induce epithelial cell migration, but effects on leukocytes have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune responses. In separate experiments we found that LAP promoted chemotaxis of human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-β1 activity. Further studies revealed that disruption of specific LAP-thrombospondin-1 (TSP-1) interactions prevented LAP-induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation

Cooling‐induced cutaneous vasodilatation is mediated by small‐conductance, calcium‐activated potassium channels in tail arteries from male mice

Abstract Cooling causes cutaneous dilatation to restrain cold‐induced constriction and prevent tissue injury. Cooling increases communication through myoendothelial gap junctions (MEGJs), thereby increasing endothelium‐derived hyperpolarization (EDH)‐type dilatation. EDH is initiated by calcium‐activated potassium channels (KCa) activated by endothelial stimuli or muscle‐derived mediators traversing MEGJs (myoendothelial feedback). The goal of this study was to determine the individual roles of KCa with small (SK3) and intermediate (IK1) conductance in cooling‐induced dilatation. Vasomotor responses of mice isolated cutaneous tail arteries were analyzed by pressure myography at 37°C and 28°C. Cooling increased acetylcholine‐induced EDH‐type dilatation during inhibition of NO and prostacyclin production. IK1 inhibition did not affect dilatations to acetylcholine, whereas SK3 inhibition inhibited dilatation at both temperatures. Cooling uncovered myoendothelial feedback to inhibit constrictions in U46619. IK1 inhibition did not affect U46619 constrictions, whereas SK3 inhibition abolished the inhibitory effect of cooling without affecting U46619 constriction at 37°C. Immunoblots confirmed SK3 expression, which was localized (immunofluorescence) to holes in the internal elastic lamina consistent with myoendothelial projections. Immunoblots and Immunofluorescence did not detect IK1. Studies in non‐cutaneous arteries have highlighted the predominant role of IK1 in EDH‐type dilatation. Cutaneous arteries are distinctly reliant on SK3, which may enable EDH‐type dilation to be amplified by cooling

Intracellular α2C-Adrenoceptors: Storage depot, stunted development or signaling domain?

AbstractG-protein coupled receptors (GPCRs) are generally considered to function as cell surface signaling structures that respond to extracellular mediators, many of which do not readily access the cell's interior. Indeed, most GPCRs are preferentially targeted to the plasma membrane. However, some receptors, including α2C-Adrenoceptors, challenge conventional concepts of GPCR activity by being preferentially retained and localized within intracellular organelles. This review will address the issues associated with this unusual GPCR localization and discuss whether it represents a novel sub-cellular niche for GPCR signaling, whether these receptors are being stored for rapid deployment to the cell surface, or whether they represent immature or incomplete receptor systems

Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166360/1/art41536_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166360/2/art41536.pd