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Decreased density of serotonin 5-HT2_A receptors in rheumatoid arthritis

¹ Department of Pharmacology and Clinical Neurosciences, Division of Clinical Pharmacology, Umeå University Hospital, Umeå, Sweden
² Department of Rheumatology, Umeå University Hospital
³ Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences, Umeå University

Correspondence to:
Correspondence to:
Dr Anders Kling
Division of Clinical Pharmacology, Umeå University Hospital, S-901 85 Umeå, Sweden; anders.kling{at}pharm.umu.se

ABSTRACT
Background: Animal studies have indicated that 5-HT2_A receptors could play a role in arthritic diseases.

Objective: To analyse the binding properties of 5-HT2_A receptors in patients with rheumatoid arthritis.

Methods: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as B_max and K_d) of 5-HT2_A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2_A receptor determine differences in receptor density.

Results: Mean of B_max of 5-HT2_A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in K_d. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in B_max between the groups.

Conclusions: The density of 5-HT2_A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.

Abbreviations: AA, adjuvant induced arthritis; [³H]LSD, [³H]-lysergic acid diethylamide; 5-HT, 5-hydroxytryptamine (serotonin)

Keywords: rheumatoid arthritis; serotonin; serotonin receptor 5-HT2A