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Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine

  • Pharmacokinetics And Disposition
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Abstract

Objective: The sulphation of the neurotransmitters dopamine and 5-hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by phenolsulphotransferases was measured in platelet homogenates prepared from a group of migraine sufferers and a group of control subjects.

Results: The activity of the M form of phenolsulpho-transferase, responsible for the sulphation of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine population, by 28% with dopamine as substrate and by 20% with 5-hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol was the same in both groups. We also report that the selective inhibition of P form phenolsulpho-transferase by red wine is much more potent than previously thought, with a 2000-fold dilution of dealcoholised red wine having the ability to inhibit sulphation by this enzyme by 50%.

Conclusion: Our findings suggest that a reduced capacity for sulphation and inactivation of biogenic amines and catecholamines may be related to susceptibility to migraine.

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Abbreviations

5-HT:

5-hydroxytryptamine

ST:

sulphotransferase

PST:

phenolsulphotransferase

M-PST:

monoamine-sulphating form of phenolsulphotransferase

P-PST:

phenol-sulphating form of phenolsulphotransferase

PAPS:

3′-phosphadenosine 5′-phosphosulphate

IC50 :

concentration resulting in 50% inhibition of enzyme activity.

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Jones, A.L., Rubin, G.L., Coughtrie, M.W.H. et al. Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine. Eur J Clin Pharmacol 49, 109–114 (1995). https://doi.org/10.1007/BF00192368

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  • DOI: https://doi.org/10.1007/BF00192368

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