1 Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells. 2 Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC 50 values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90+0.20 mM; human=1.90+0.30 mM: CHO cells: rat=0.20+0.06 mM; human=0.19+0.08 mM). 3 In CHO cell lines co-expressing either rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the EC 50 values for capsaicin-induced responses were similar in both cell lines (rat=0.35+0.06 mM, human=0.53+0.03 mM). 4 The threshold for activation by acidic solutions was lower for human VR1 channels than that for rat VR1 (EC 50 pH 5.49+0.04 and pH 5.78+0.09, respectively). 5 The threshold for heat activation was identical (428C) for rat and human VR1. 6 PPAHV was an agonist at rat VR1 (EC 50 between 3 and 10 mM) but was virtually inactive at the human VR1 (EC 50 410 mM). 7 Capsazepine and ruthenium red were both more potent at blocking the capsaicin response of human VR1 than rat VR1. 8 Capsazepine blocked the human but not the rat VR1 response to low pH. Capsazepine was also more e ective at inhibiting the noxious heat response of human than of rat VR1.

Parkinson's disease (PD) has been associated with exposure to a variety of environmental agents, including pesticides, heavy metals, and organic pollutants; and inflammatory processes appear to constitute a common mechanistic link among these insults. Indeed, toxin exposure has been repeatedly demonstrated to induce the release of oxidative and inflammatory factors from immunocompetent microglia, leading to damage and death of midbrain dopamine (DA) neurons. In particular, proinflammatory cytokines such as tumor necrosis factor-α and interferon-γ, which are produced locally within the brain by microglia, have been implicated in the loss of DA neurons in toxin-based models of PD; and mounting evidence suggests a contributory role of the inflammatory enzyme, cyclooxygenase-2. Likewise, immune-activating bacterial and viral agents were reported to have neurodegenerative effects themselves and to augment the deleterious impact of chemical toxins upon DA neurons. The present paper will focus upon the evidence linking microglia and their inflammatory processes to the death of DA neurons following toxin exposure. Particular attention will be devoted to the possibility that environmental toxins can activate microglia, resulting in these cells adopting a “sensitized” state that favors the production of proinflammatory cytokines and damaging oxidative radicals.

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The point source RX J0007.0+7302, at the center of supernova remnant CTA 1, was studied using the X-Ray Multi-mirror Mission (XMM-Newton). The X-ray spectrum of the source is consistent with a neutron star interpretation, and is well described by a power law with the addition of a soft thermal component that may correspond to emission from hot polar cap regions or to cooling emission from a light element atmosphere over the entire star. There is evidence of extended emission on small spatial scales which may correspond to structure in the underlying synchrotron nebula. No pulsations are observed. Extrapolation of the nonthermal spectrum of RX J0007.0+7302 to gamma-ray energies yields a flux consistent with that of EGRET source 3EG J0010+7309, supporting the proposition that there is a gamma-ray emitting pulsar at the center of CTA 1. Observations of the outer regions of CTA 1 with the Advanced Satellite for Cosmology and Astrophysics confirm earlier detections of thermal emission from the remnant and show that the synchrotron nebula extends to the outermost reaches of the SNR. Subject headings: stars: neutron -stars: individual (RX J0007.0+7302, 3EG J0010+7309) -ISM: individual (CTA 1) -supernova remnants -X-rays: ISM