Lincoln Edwards, PhD Dept. of Physiology/Pharmacology
Risley Hall Room 101
School of medicine, Loma Linda University
Loma Linda CA 92350
Phone: Office (909) 558-1000, extension 42923
Phone: Lab (909) 558-1000, extension 47035
Email: lpedwards@llu.edu
Basic and clinical research support imidazoline compounds (clonidine and other related centrally-acting antihypertensive agents) as potential candidate drugs to treat Metabolic Syndrome X and type 2 diabetes. Our primary focus is to determine the molecular mechanism(s) by which imidazoline compounds reduce insulin resistance, improve glucose disposal rates, lower blood pressure, and cause vascular contraction. The possible cross-talk between insulin and imidazoline receptor signaling pathways is a possible mechanism by which imidazoline compounds exert their anti-diabetic properties. We employ a number of techniques to study imidazoline receptor signaling such as Western blotting, microarray, RNA-interference, immunoprecipitation, and calcium imaging. Cell types that have imidazoline receptors are used as model systems. These include PC12 (adrenal pheochromocytoma) cells and HepG2 (liver) cells. Effects of imidazoline compounds on blood pressure is studied by microinjection of these compounds into the medulla region of rat brain while continuously monitoring blood pressure. Vascular effects of imidazoline compounds are studied using rat arterial ring preparations in a bath system, connected to a computer via a force transducer. This is an exciting time to be part of our research efforts as we are testing novel imidazoline compounds that hold great promise, not only as therapeutic agents for type 2 diabetes and Metabolic Syndrome X, but also as selective ligands for the I 1-imidazoline receptors.
George, O. K., Gonzalez, R. R., and Edwards, L. P. (2003). Moxonidine, a selective α 2-adrenergic and Imidazoline receptor Agonist, is permissive to α 1-adrenergic receptor pathway in the rat-tail artery. J. of Cardiovascular Pharmacology 43(2):306-311.
Edwards, L. P., and Ernsberger, P: The I 1-imidazoline Receptor in PC12 Pheochromocytoma Cells Reverses NGF-Induced ERK Activation and Induces MKP-2 Phosphatase. Brain Research (2003) 980(1):71-79
Edwards L. P., Fishman D, Horowitz P, Bourbon N, Kester M, Ernsberger P. The I 1-imidazoline receptor in PC12 pheochromocytoma cells activates protein kinases C, extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK). J. Neurochem (2001) 79(5):931-940
Edwards, L.P., and Ernsberger, P. (2000) Assay of Arachidonic Acid Release Coupled to α 1- and α 2-Adrenergic Receptors, in Methods in Molecular Biology, vol.126. (Adrenergic Receptor Protocols Curtis A. Machida editor), Humana Press, Totowa, New Jersey, pg. 375 – 390
Edwards, L. P., Whitter, E. and Hessinger, D. Apparent membrane pore-formation by Portuguese Man-of-war (Physalia physalis) venom in intact cultured cells.. Toxicon 40 (2002 ) 1299-1305
Edwards, L. P., Luo, E., Hall, R., Gonzalez Jr.,R.R. and Hessinger, D.A. The Effect of Portuguese Man-of-war (Physalia physalis) venom on calcium, sodium and potassium fluxes of cultured embryonic chick heart cells. Toxicon (2000)Mar; 38(3): 323-335
Edwards, L. P., and Hessinger, D. Portuguese Man-of-war (Physalia physalis) venom induces calcium influx into cells by permeabilizing plasma membranes. Toxicon 2000 Aug; 38(8):1015-28
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Last Revised: Tue, Jul 11, 2006