Taiji Yoshino

A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes

In nonexcitable cells, Ca2+ entry is mediated predominantly through the store depletion-dependent Ca2+ channels called store-operated Ca2+ (SOC) or Ca2+ release-activated Ca2+ channels. YM-58483, a pyrazole derivative, inhibited an anti-CD3 mAb-induced sustained Ca2+ influx in acute T cell leukemia, Jurkat cells. But it did not affect an anti-CD3 mAb-induced transient intracellular Ca2+ increase in Ca2+-free medium, nor anti-CD3 mAb-induced phosphorylation of phospholipase Cγ1. It was suggested that YM-58483 inhibited Ca2+ influx through SOC channels without affecting the TCR signal transduction cascade. Furthermore, YM-58483 inhibited thapsigargin-induced sustained Ca2+ influx with an IC50 value of 100 nM without affecting membrane potential. YM-58483 inhibited by 30-fold the Ca2+ influx through SOC channels compared with voltage-operated Ca2+ channels, while econazole inhibited both SOC channels and voltage-operated Ca2+ channels with an equivalent range of IC50 values. YM-58483 potently inhibited IL-2 production and NF-AT-driven promoter activity, but not AP-1-driven promoter activity in Jurkat cells. Moreover, this compound inhibited delayed-type hypersensitivity in mice with an ED50 of 1.1 mg/kg. Therefore, we concluded that YM-58483 was a novel store-operated Ca2+ entry blocker and a potent immunomodulator, and could be useful for the treatment of autoimmune diseases and chronic inflammation. Furthermore, YM-58483 would be a candidate for the study of capacitative Ca2+ entry mechanisms through SOC/CRAC channels and for identification of putative Ca2+ channel genes.

Study on Physiological Roles of Stimulation of Prostaglandin E2 Receptor Subtype EP2 in Urethral Function in Rats.

We investigated the relaxant effect of stimulation of prostaglandin E2 (PGE2) receptor subtype EP2 as well as the involvement of a cyclic AMP (cAMP)‐dependent pathway related to stimulation of EP2 receptors in urethral function in rats by evaluating effects of PGE2 and selective EP2 receptor agonist CP‐533,536.

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP‐533,536 on voiding efficiency in rats with midodrine‐induced functional urethral obstruction.

Intratesticular Bradykinin Involvement in Rat Testicular Pain Models

To clarify the role of bradykinin in urogenital pain, we investigated bradykinin involvement in rat models of testicular pain.

Physiological Roles of Bradykinin and Involvement of Bradykinin B2 Receptor in Urethral Function in Humans and Animals.

We investigated the role of bradykinin in urethral function by examining contractile responses in urethral smooth muscle strips isolated from humans and the intraurethral pressure in rats and dogs.