Research Project
2253013
DESCRIPTION: (Adapted from Applicant's Abstract) Nitric oxide (NO) is a free-radical gas that is implicated in many important physiological roles, including such fundamental processes as blood pressure regulation and memory formation. While much indirect research has been performed on systems that use NO, studies of direct in vivo application of NO have been hindered by the volatility of NO and the potential toxicity of currently-used methods of delivering it. A new method for delivering NO is proposed, based on the availability of new, "caged" compounds. These substances conserve their biological activity until activated with light stimuli of the appropriate wavelength. A sequential, three stage experimental approach will be employed to prove the feasibility of the method, culminating in the demonstration of feasibility in an experimental animal model. In addition to enabling NO delivery in an animal with intact neuronal and vascular circuits, the method will apply to other neurotransmitters. Based on the design flexibility, a wide range of potential applications are envisioned: in micropharmacology experiments (where the delivery method promises better temporal resolution and receptor coverage than currently available micropharmacological techniques, including microiontophoresis and pressure ejection); in new in vivo and in vitro macropharmacological approaches; and in new photodynamic cancer therapies.
