Anandamide, an endogenous cannabinoid ligand, binds to CB1 cannabinoid receptors in the brain and mimics the neurobehavioural actions of marijuana. Cannabinoids and anandamide also elicit hypotension mediated by peripheral CB1 receptors. Here we report that a selective CB1 receptor antagonist, SR141716A, elicits an increase in blood pressure in rats subjected to haemorrhagic shock, whereas similar treatment of normotensive rats or intracerebroventricular administration of the antagonist during shock do not affect blood pressure. Blood from haemorrhaged rats causes hypotension in normal rats, which can be prevented by SR141716A but not by inhibition of nitric oxide synthase in the recipient. Macrophages and platelets from haemorrhaged rats elicit CB1 receptor-mediated hypotension in normotensive recipients, and incorporate arachidonic acid or ethanolamine into a product that co-elutes with anandamide on reverse-phase high-performance liquid chromatography. Also, macrophages from control rats stimulated with ionomycin or bacterial phospholipase D produce anandamide, as identified by gas chromatography and mass spectrometry. These findings indicate that activation of peripheral CB1 cannabinoid receptors contributes to haemorrhagic hypotension, and anandamide produced by macrophages may be a mediator of this effect.
The field of nanotechnology is rapidly expanding with the development of novel nanopharmaceuticals that have potential for revolutionizing medical treatment. The rapid pace of expansion in this field has exceeded the pace of pharmacological and toxicological research on the effects of nanoparticles in the biological environment. The development of cadmium-containing nanoparticles, known as quantum dots, show great promise for treatment and diagnosis of cancer and targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. However information on pharmacology and toxicology of quantum dots needs much further development, making it difficult to assess the risks associated with this new nanotechnology. Further, nanotechnology poses yet another risk for toxic cadmium, which will now enter the biological realm in nano-form. In this review, we discuss cadmium-containing quantum dots and their physicochemical properties at the nano-scale. We summarize the existing work on pharmacology and toxicology of cadmium-containing quantum dots and discuss perspectives in their utility in disease treatment. Finally, we identify critical gaps in our knowledge of cadmium quantum dot toxicity, and how these gaps need to be assessed to enable quantum dot nanotechnology to transit safely from bench to bedside.
Activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is implicated in the pathophysiology of traumatic brain injury. Here, the effects of mechanical injury on the voltage-dependent magnesium (Mg2+) block of NMDA currents in cultured rat cortical neurons were examined. Stretch-induced injury was found to reduce the Mg2+ blockade, resulting in significantly larger ionic currents and increases in intracellular free calcium (Ca2+) concentration after NMDA stimulation of injured neurons. The Mg2+ blockade was partially restored by increased extracellular Mg2+ concentration or by pretreatment with the protein kinase C inhibitor calphostin C. These findings could account for the secondary pathological changes associated with traumatic brain injury.
Nanotechnology has made significant advances in the reduction of free radical damage in the field of materials science. Cross-disciplinary interactions and the application of this technology to biological systems has led to the elucidation of novel nanoparticle antioxidants, which are the subject of this review. Recent reports suggest that cerium oxide and other nanoparticles are potent, and probably regenerative, free radical scavengers in vitro and in vivo. The neuroprotective, longevity-enhancing and anti-inflammatory properties of nanoparticles are summarized and hypotheses regarding their unique mechanism of action are presented. The chemical and physical properties of antioxidant nanoparticles are discussed in an interdisciplinary manner, with emphasis on biological properties and biomedical applications. Additionally, the need for alterations in traditional pharmacological parameters of dose and absorption, distribution, metabolism, and excretion are discussed and future directions necessary for bringing nanoparticle antioxidants into the realm of clinical reality are presented.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.