Zaltoprofen inhibits bradykinin-mediated enhancement of glutamate receptor activity in substantia gelatinosa neurons.

Abstract

Zaltoprofen, a propionic acid derivative of nonsteroidal anti-inflammatory drugs, has been proposed to inhibit the nociception mediated by bradykinin. Here, I attempted to clarify the molecular mechanisms underlying the blocking effect of zaltoprofen on bradykinin-mediated enhancement of excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord. The effects of zaltoprofen on the response to exogenous administration of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) currents were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. AMPA currents were significantly enhanced by preapplication of bradykinin (10 μM). However, zaltoprofen (1, 10 μM) and a nonselective cyclooxygenase (COX)-1 and COX-2 inhibitor, ibuprofen, blocked the bradykinin-mediated enhancing effect. The inhibitory effect of ibuprofen, but not zaltoprofen, was removed by adding prostaglandin E(2). Furthermore, the inhibitory effect of zaltoprofen was removed in the presence of protein kinase C (PKC) activator, whereas the effect of zaltoprofen was still present in the presence of phospholipase C activator. These findings suggest that the antinociceptive effect of zaltoprofen may block the augmenting effect of bradykinin on AMPA currents through inhibition of protein kinase C activation, without affecting COX in the superficial dorsal horn.