The effect of selective type A or type B monoamine oxidase inhibition on the intrasynaptosomal deamination of (3H)serotonin in rat spinal cord tissue.
The degree to which the type A and type B forms of monoamine oxidase participate in the intraneuronal deamination of (3H)serotonin (5-HT) was examined in synaptosomal-rich fractions of rat spinal cord tissue. Synaptosomes were labeled with (3H)5-HT and superfused with physiological buffers containing selective concentrations of a type A (clorgyline) or a type B (deprenyl) MAO inhibitor. The efflux of (3H)5-HT and newly-formed (3H)5-hydroxyindoleacetic acid (5-HIAA) was determined and compared to controls over time. In control samples, a slight decline in (3H)5-HT efflux occurred over the experimental superfusion period. However, a stable formation and efflux of (3H)5-HIAA was seen during this same period of time. When clorgyline was added to the superfusion buffer, a rapid decline in superfusate levels of (3H)5-HIAA was observed. Similar experiments in the presence of deprenyl were without effect. In order to elevate cytoplasmic concentrations of (3H)5-HT and therefore increase its chances for interaction with nerve terminal MAO, reserpine was added to the superfusion buffer. Reserpine caused a greater than 3-fold increase in (3H)5-HIAA formation with no change in (3H)5-HT efflux. Clorgyline inhibited this increase in (3H)5-HIAA formation but deprenyl was again without effect. In the presence of clorgyline, reserpine also caused an increase in (3H)5-HT efflux. These results strongly support the notion that 5-HT deamination within rat spinal cord nerve terminals occurs primarily, if not exclusively, through an interaction with type A MAO.
Azzaro
A J
AJ
Department of Anesthesiology, West Virginia University Medical Center, Morgantown 26506.
Amedro
J B
JB
Brown
L M
LM
Smith
D J
DJ
Williams
G M
GM
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D003641:Deamination; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003010:Clorgyline