Abstract
Two tetrapeptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified as endogenous ligands for the μ-opioid receptors. In order to clarify details of the actions of EM-1 and EM-2 on nociceptive transmission, we examined their effects on synaptic transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole-cell patch-clamp technique. Each of EM-1 and EM-2 produced outward currents at -70 mV in a dose-dependent manner (EC50 = 0.13 μM and 0.15 μM, respectively). Currents induced by them reversed their polarity at potentials which were close to the equilibrium potential for K+, and were reduced in amplitude by a μ-opioid receptor antagonist, CTAP (1 μM). Spontaneous glutamatergic excitatory postsynaptic currents decreased in frequency by EM-1 and EM-2 (1 μM, each) to about 50％ of control with no notable change in the amplitude in almost all neurons tested. Glycinergic and GABAergic focally-evoked inhibitory postsynaptic currents were reduced in amplitude by EM-1 and EM-2 (1 μM, each) to about 50% of control. It is concluded in SG neurons that endomorphins hyperpolize membranes by opening K+ channels, and depress excitatory and inhibitory transmission through the activation of μ-opioid receptors; these actions would contribute to at least a part of the modulation of nociceptive transmission in the spinal dorsal horn. [Jpn J Physiol 54 Suppl:S156 (2004)]
