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A M Dodson

Publications and source records attributed to A M Dodson.

4 recordsLinked to original sources
PubMed2004

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.

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PubMed2001

Bradykinin increases Na(+)-K(+) pump activity in cultured guinea-pig tracheal smooth muscle cells.

1. The effect of bradykinin on the Na+-K+ pump of airway smooth muscle was investigated by measuring ouabain-sensitive (86)Rb(+) uptake in cultured guinea-pig tracheal smooth muscle cells. 2. Bradykinin induced a concentration-dependent increase in ouabain-sensitive (86)Rb(+) uptake, with an EC(50) of 3 nM (pD(2) = 8.50+/-0.10). Stimulation was not affected by indomethacin (1 microM) suggesting that it is not mediated by cycloxygenase products of arachidonic acid. 3. The B(1) receptor agonists Lys-des-Arg(9)-bradykinin and des-Arg(9)-bradykinin had no effect on ouabain-sensitive (86)Rb(+) uptake. In contrast, the B(1) and B(2) receptor agonist Lys-bradykinin induced a concentration-dependent increase in ouabain-sensitive (86)Rb(+) uptake with an EC(50) of 6 nM (pD(2) = 8.21 +/- 0.20). 4. The B(1) receptor antagonist des-Arg(10)-HOE 140 (1 microM) had no effect on bradykinin-stimulated ouabain-sensitive (86)Rb(+) uptake. The B(2) receptor antagonists HOE 140 and WIN 64338 antagonized bradykinin-stimulated ouabain-sensitive (86)Rb(+) uptake with pK(B) values (-log M) of 8.20 +/- 0.08 and 8.11 +/- 0.20 respectively. 5. Reducing extracellular Na+ from 146 mM to 11 mM caused a 53.5% decrease in basal ouabain-sensitive (86)Rb+ uptake and abolished bradykinin-induced uptake. Two inhibitors of the Na(+)-H(+) exchanger, methylisobutyl-amiloride (MIA; 1 - 100 microM) and ethylisopropyl-amiloride (EIPA; 0.1 - 10 microM), inhibited bradykinin-stimulated ouabain-sensitive (86)Rb(+) uptake without affecting basal uptake. 6. These results suggest that bradykinin increases Na+-K+ pump activity of guinea-pig tracheal smooth muscle via stimulation of B(2) receptors and activation of the Na+-H+ exchanger.

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PubMed2000

Stimulation of the Na(+)-K(+) pump in cultured guinea pig airway smooth muscle cells by serotonin.

The effect of 5-hydroxytryptamine (5-HT) or serotonin on Na(+)-K(+) pump activity of airway smooth muscle was investigated by measuring (86)Rb(+) uptake in cultured guinea pig tracheal smooth muscle cells. (86)Rb(+) uptake consisted of three distinct components, one sensitive to ouabain, one to bumetanide, and one insensitive to either inhibitor. 5-HT induced a concentration-dependent increase in ouabain-sensitive (86)Rb(+) uptake (EC(50) = 21 nM) but had no effect on bumetanide-sensitive uptake, suggesting that it stimulates the Na(+)-K(+) pump but not the Na(+)-K(+)-Cl(-) cotransporter. Ouabain-sensitive uptake also was stimulated by the 5-HT(2A/2C) agonists 2,5-dimethoxy-4-iodoamphetamine and alpha-methyl-5-HT, but not by the 5-HT(1) agonist 5-carboxamidotryptamine, the 5-HT(1A/1B/2C) agonist 1-(3-chlorophenyl)piperazine, or the 5-HT(3) agonist 1-(3-chlorophenyl)biguanide. 5-HT-stimulated (86)Rb(+) uptake was inhibited by the 5-HT(2A) antagonists ketanserin and spiperone, but not by the 5-HT(1A) antagonist NAN 190 or the 5-HT(3) antagonist Y25310. 5-HT-stimulated (86)Rb(+) uptake was inhibited by reducing extracellular Na(+) concentration and by the Na(+)-H(+) exchange inhibitors dimethylamiloride and 5-(N-methyl-N-isobutyl)-amiloride. These observations suggest that 5-HT stimulates the Na(+)-K(+) pump of airway smooth muscle via 5-HT(2A) receptors by a mechanism dependent on Na(+) influx, possibly through the Na(+)-H(+) exchanger. Because stimulation of the Na(+)-K(+) pump produces hyperpolarization, this may represent a negative-feedback mechanism that opposes contraction in response to 5-HT.

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