Nonintracellular, cell-associated O-methylation of isoproterenol in the isolated rabbit thoracic aorta

Journal Article · Mon Jul 01 04:00:00 EDT 1985 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5180236

Head, R J; Irvine, R J; Barone, S; Stitzel, R E; de la Lande, I S

The present study examines the subcellular site of catecholamine O-methylation in extraneuronal tissue. S-Adenosyl-l-methionine, a methyl donor that does not diffuse across biological membranes, was used to assess the participation of plasma membrane bound catechol-O-methyltransferase vs. cytoplasmic catechol-O-methyltransferase in the catecholamine O-methylating process. Segments of rabbit thoracic aorta incubated with (methyl-/sup 3/H)-S-adenosyl-l-methionine and isoproterenol generate (/sup 3/H)methoxy-isoproterenol. The formation of (/sup 3/H)methoxy-isoproterenol from (methyl-/sup 3/H)-S-adenosyl-l-methionine was proportional to the isoproterenol concentrations in the range of 0.1 to 1.0 microM. There was a marked preference for the O-methylation of the (+)- rather than the (-)-isomer of isoproterenol. The O-methylation of isoproterenol in the presence of (methyl-/sup 3/H)-S-adenosyl-l-methionine was stimulated as much as 8-fold by the removal of calcium ions from the incubation solutions. In contrast, the O-methylation of (+)-(/sup 3/H)isoproterenol by endogenous, intracellular S-adenosyl-l-methionine was only slightly inhibited by the removal of calcium ions from incubation solutions. The formation of (/sup 3/H)methoxy-isoproterenol from (methyl-/sup 3/H)-S-adenosyl-l-methionine and isoproterenol was not inhibited by pretreatment of tissues with phenoxybenzamine (32 microM) or treatment with metanephrine (27 mumol 1(-1) or deoxycorticosterone acetate (27 microM), i.e., drug treatments that inhibit the extraneuronal uptake and O-methylation of (/sup 3/H)-isoproterenol by endogenous intracellular S-adenosyl-l-methionine. The results of this study provide evidence for a nonintracellular, cell-associated site of O-methylation of isoproterenol in the rabbit aorta.

• Research Organization: West Virginia Univ. Medical School, Morgantown
• OSTI ID: 5180236
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 1; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
AMINES
ANIMALS
AORTA
AROMATICS
ARTERIES
BLOOD VESSELS
BODY
CALCIUM
CARDIOVASCULAR SYSTEM
CATECHOLAMINES
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL REACTIONS
ELEMENTS
ENZYME ACTIVITY
ENZYMES
HYDROXY COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
METALS
METHYLATION
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
RABBITS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES