Methotrexate Induces Hyperplasia of Enterochromaffin Cells in Mouse Jejunum

Abstract

5-Hydroxytryptamine (5-HT) is synthesized by L-tryptophan hydroxylase (TPH) and is stored mainly in enterochromaffin cells of the mucosal epithelium. We previously reported that administration of methotrexate, an anticancer agent, to rats caused hyperplasia of enterochromaffin cells, and nitric oxide (NO) might be involved in the underlying mechanism. The aim of this study was to clarify the effect of methotrexate on hyperplasia of enterochromaffin cells in mice. C57BL/6J mice were intraperitoneally injected with methotrexate or saline as a control. Methotrexate caused an increase in the number of TPH-expressing cells (i.e., enterochromaffin cells) in the jejunum. Methotrexate also increased inducible, but not constitutive, NOS mRNA expression. Our results indicate that methotrexate potentiates 5-HT synthesis in mice, as we previously found in rats.

The platelet serotonergic system and the search for new biomarkers and therapeutic options for diverse diseases

“…After binding with 5-HT2A, 5-HT is released into the bloodstream, resulting in the activation of nearby platelets and greater platelet aggregation to form thrombi during the inflammatory response. Moreover, there is evidence of a vasoconstrictor effect elicited by the activation of 5-HT2A receptors in cells of vascular smooth muscle cells, and a vasodilator effect stemming from the activation of 5-HT1B in endothelial cells through a mechanism dependent on nitric oxide (NO) [47].…”

“…There are few reports on the function of 5-HT1B/1D subtypes. A study based on a rat model suggests that their activation may produce vasodilation and a drop in blood pressure [47,52].…”