Serotonin uptake and metabolism by cultured guinea pig airway smooth muscle cells.
Serotonin (5-hydroxytryptamine, 5-HT) is synthesized and released in the airways by pulmonary neuroendocrine cells located in the vicinity of airway smooth muscle (ASM). The aim of this study was to determine whether ASM cells contribute to the inactivation of serotonin, and investigate the role of the serotonin transporter (SERT) and monoamine oxidase (MAO) in this process. Cultured guinea pig tracheal smooth muscle cells, maintained in culture medium containing serotonin for 1-4 days, induced a decrease in 5-HT and increase in 5-HIAA in the culture medium. Changes in indole concentrations were prevented by fluvoxamine and iproniazid. Na+-sensitive [3H]-serotonin uptake into cultured ASM cells was time- and concentration-dependent (Km, 561 nM; Vmax, 1.06 pmol/mg protein/min), and inhibited by clomipramine (IC50, 13.7 nM), fluvoxamine (IC50, 0.16 microM) and fluoxetine (IC50, 0.32 microM). Western blot analysis with an anti-SERT antibody revealed a single 115 kDa immunoreactive band in ASM cell lysates. The results of this study suggest that ASM contributes to the uptake and metabolism of serotonin via SERT and MAO, respectively, and may therefore play a role in the inactivation of endogenous serotonin generated within the airway wall.
Dodson
A M
AM
John B Pierce Laboratory, 290 Congress Avenue, New haven, CT 06519, USA.
Anderson
G M
GM
Rhoden
K J
KJ
D000818:Animals; D002478:Cells, Cultured; D002997:Clomipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D002997:Clomipramine; D005473:Fluoxetine; D016666:Fluvoxamine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors