Superoxide anion (O 2 ؊ ) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated in the development of hypertension. In previous studies, we found that O 2 ؊ is produced predominantly in the adventitia of isolated rabbit aorta and acts as a barrier to NO. In the present studies, we characterize the enzyme responsible for O 2 ؊ production in the adventitia and show that this enzyme is a constitutively active NADPH oxidase with similar composition as the phagocyte NADPH oxidase. Constitutive O 2 ؊ -generating activity was localized to aortic adventitial fibroblasts and was enhanced by the potent vasoconstrictor angiotensin II. Immunohistochemistry of aortic sections demonstrated the presence of p22 phox , gp91 phox , p47 phox , and p67 phox localized exclusively in rabbit aortic adventitia, coincident with the site of staining for O 2 ؊ production. Furthermore, immunodepletion of p67 phox from adventitial fibroblast particulates resulted in the loss of NADPH oxidase activity, which could be restored by the addition of recombinant p67 phox . Further study into the regulation of this adventitial source of O 2 ؊ is important in elucidating the mechanisms regulating the bioactivity of NO and may contribute to our understanding of the pathogenesis of hypertension.In recent years, reactive oxygen species (ROS) such as superoxide anion (O 2 Ϫ ) have been shown to play a number of roles in the body. Phagocytic cells produce ROS as a primary host defense mechanism (1), whereas other cells utilize ROS as intracellular second messengers for a wide range of cellular functions. For example, ROS participate in Ras-mediated mitogenic signaling in fibroblasts as well as in leukocyte apoptosis (2, 3).The phagocyte NADPH oxidase or respiratory burst oxidase is the best characterized ROS-generating system and is a multicomponent enzyme complex that catalyzes the oneelectron reduction of oxygen to O 2 Ϫ . Its components include the two membrane-spanning polypeptides, p22 phox and gp91 phox , which comprise flavocytochrome b 558 , and three cytoplasmic polypeptides, p40 phox , p47 phox , and p67 phox (4-6). Additionally, the cytosolic guanine nucleotide-binding protein Rac2 is required for oxidase activation (7). Exposure of the cell to a variety of agonists induces the association of the cytosolic with the membrane-associated components and causes activation of the normally dormant oxidase (4-6).Several groups have shown that NAD(P)H oxidase(s) exist in nonphagocytic cells including carotid body (8), mesangial cells (9), vascular smooth muscle cells (10, 11), endothelial cells (12, 13), and fibroblasts (14). The NAD(P)H oxidase systems in these cells have not yet been well characterized, and even the substrate specificity of these oxidase(s) with regard to NADH and NADPH is still not clear (10)(11)(12)15). In vascular smooth muscle cells of the bovine pulmonary artery and rat aorta, an NADH oxidase has been described, and in the rat aorta these cells express...

A series of per-6-substituted cyclodextrin derivatives was synthesized as synthetic host molecules for rocuronium, a steroidal muscle relaxant. By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo. The isothermal microcalorimetry data are consistent with the biological data supporting the encapsulation mechanism of action. Binary and biphasic complexes are reported with NMR experiments clearly showing free and bound rocuronium. [structure: see text]

1 2 EPSP-Spike (E-S) Potentiation occurs alongside synaptic Long-Term Potentiation 3 (LTP), both triggered by high-frequency synaptic stimulation (HFS). In this study, we 4 confirm the earlier findings that E-S potentiation appears to be prevented by prior 5 reduction of GABAA receptor-mediated inhibitory synaptic transmission. However, we 6 demonstrate that this is a result of an occlusion of E-S potentiation, not a block. E-S 7 potentiation and GABAA antagonism each saturate postsynaptic action potential 8 discharge, but E-S potentiation can still be induced by high frequency activation of 9 synapses, even in the presence of pharmacological GABAA blockade. These results 10 suggest that GABAA blockers/antagonists and E-S potentiation share an expression 11 mechanism, namely the reduction of GABAA-mediated synaptic inhibition. We also 12 assayed changes in the electrical coupling between dendrite and soma, and were 13 surprised to find that this coupling is decreased following HFS, a change that would 14 oppose E-S potentiation. This decrease in dendritic-soma electrical coupling (D-S 15 coupling) was induced through the action of GABAB receptors, but not maintained or 16 expressed via the activity of these receptors. These data all together suggest that there 17 are two distinct and opposing changes that occur as a result of HFS: 1) A decrease in 18 passive dendro-somatic electrical coupling, and 2), an increase in coupling between the 19 somatic EPSP and action potential generation. These two opposing influences may 20 function as a homeostatic mechanism to balance the excitatory/inhibitory relationship 21 between primary neurons and interneurons, and may represent a separate mechanism 22 by which feedback and feed-forward synaptic inhibition can influence E-S coupling in 23 opposite directions. 24 25 26