Potent and selective. cap alpha. /sub 2/-adrenoceptor by L-657,743, a new spirocyclic-substituted benzofuroquinolizine

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5451099

Pettibone, D J; Clineschmidt, B V; Lotti, V J; Baldwin, J J; Desolms, S J; Guare, J P; Huff, J R; Randall, W C; Vacca, J; Young, S D

In the rat vas deferens, neuronal deamination of /sup 3/H-(-)noradrenaline (/sup 3/H-NA) to /sup 3/H-dihydroxyphenethylglycol (/sup 3/HDOPEG) cannot be inhibited by pretreatment with a monoamine oxidase (MAO) inhibitor. However, in the extraneuronal compartment of the rat heart. However, in the extraneuronal compartment of the rat heart, inhibition of MAO abolishes the formation of /sup 3/HDOPEG. To clarify this discrepancy, the authors determined the rate constant for MAO (/sup k/mao) neuronally (rat vas deferens) and extraneuronally (rat heart). For neuronal /sup k/mao/, vasa deferentia were incubated with /sup 3/HNA for 300 minutes, and the cumulative formation of /sup 3/HDOPEG measured. The delay in time before /sup 3/HDOPEG achieves steady state (/sup tau/system), is inversely proportional to /sup k/mao/. Because /sup tau/system is very short for neuronal MAO, an appreciable delay was only achieved after partial inhibition of MAO with various pargyline concentrations. To relate to the uninhibited enzyme, the percentage inhibition by pargyline was then determined in homogenate preparations. For extraneuronal MAO, a similar procedure was performed in perfused rat hearts. Results show a significantly greater /sup k/mao of neuronal origin, (/sup k/mao = .57 min /sup -/1) which when related to the fractional size of the neuronal compartment suggests a very high activity of neuronal MAO.

• Research Organization: Merck Sharp and Dohme Research Labs., West Point, PA
• OSTI ID: 5451099
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

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550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
DRUGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANES
NERVOUS SYSTEM
ORGANS
RATS
REACTION KINETICS
RODENTS
SYMPATHOLYTICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES