抄録
It has been reported that an anandamide (endocannabinoid)-transport inhibitor AM404 activates cloned vanilloid TRPV1 (which is also known as VR1) receptors. In order to address this issue in the spinal dorsal horn, we examined the effect of AM404 (30μM) on spontaneous glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole-cell patch-clamp technique. In 84% of the SG neurons examined (n = 44), AM404 reversibly increased the frequency of spontaneous excitatory postsynaptic current (sEPSC; by 68 ± 7% at 2 min after the beginning of AM404 superfusion) in a manner similar to that of capsaicin. AM404 was without actions in the presence of a TRPV1 receptor antagonist capsazepine (10μM). On the other hand, sEPSC amplitude and also a response of SG neurons to AMPA (5μM) were not affected by AM404. These results indicate that AM404 enhances the spontaneous release of L-glutamate by activating TRPV1 receptors in the SG. We conclude that when AM404 is used as an anandamide-transport inhibitor in the SG, its TRPV1 receptor activation also have to be taken into consideration. [Jpn J Physiol 55 Suppl:S145 (2005)]
