title: Modulation of NA-synthase activity in rat cortex using NA measurement with ultramicro carbon electrode following topical applications of pharmacological agents.
abstract: The aim of the study was to document NA, the active product of brain NA-synthase known as NO-synthase in rat cortex. NA measurements in brain extracellular fluid were performed using an ultramicro carbon electrode (0.5-2 microm) with differential pulse voltammetry. The ultramicro carbon electrode was inserted at a fixed depth (125 microm) into the frontal cortex. A constant level of neuronal NA (0.66 mM) was found in rat cortex during a few hours in the basal state. Topical applications of competitive inhibitors of brain NO-synthase (L-NNA, L-NMA, D-arginine, 1 mg ml(-1)) and a NO-donor (SNAP, 1 mg ml(-1)) resulted in a complete disappearance of NA. Simultaneous in vivo measurements of L-NNA, an electroactive inhibitor (-1.2 V vs. Ag/AgCl), and NA (-1.66 V vs. Ag/AgCl) allowed the following of the diffusion of this neuronal specific inhibitor and the simultaneous inhibition of NA synthesis. Topical addition of acetylcholine (10 microM) produced a NA increase, while bradykinin, adenosine, and hydrogen peroxide (10 microM each) resulted in the disappearance of NA. Topical addition of radical oxygen species (ROS) scavengers (oxy-hemoglobin, methylen blue, ascorbic acid and cystein, l mg ml(-1)) had no influence on NA concentrations which remained at a constant level in brain cortex. These preliminary results indicated that NA is continuously produced at a high level by neurons. Acetylcholine and vasodilatators modulated neuronal NA synthesis after topical application, but ROS had no effect.
authors.affiliation: Laboratoire de Biophysique, Faculté de Médecine Xavier Bichat, 16 rue H. Huchard, 75018 Paris, France. alain.meulemans@voila.fr
authors.forename: A
authors.initials: A
authors.lastname: Meulemans
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D002244:Carbon; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008839:Microelectrodes; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009603:Nitroso Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C084185:N-nitrosoarginine; D002244:Carbon; D001120:Arginine; D019001:Nitric Oxide Synthase