Alpha-2 adrenoceptor mediating the facilitatory effect of norepinephrine on the glycine response in the spinal dorsal horn neuron of the rat

Effects of norepinephrine (NE) on the glycine-mediated inhibitory response were investigated in neurons acutely dissociated from the rat spinal dorsal horn, using nystatin perforated patch recording mode under voltage-clamp conditions. NE reversibly and concentration dependently facilitated Cl(-) current induced by 3 x 10(-5) M glycine. NE neither changed the reversal potential of the glycine response nor affected the affinity of glycine to its receptor. This effect could be mimicked by clonidine (10(-7) M) and blocked by yohimbine (10(-6) M), respectively. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-89), an inhibitor of protein kinase A, effectively mimicked the effect of NE on glycine response, whereas chelerythrine (an inhibitor of protein kinase C) failed. NE further enhanced glycine response even in the presence of chelerythrine or stearoylcarnitine chloride (another inhibitor of protein kinase C) or chelerythrine together with stearoylcarnitine chloride. The present results suggest that alpha2-adrenoceptor is involved in the potentiation of NE on glycine response in freshly isolated spinal dorsal horn neurons. Activation of alpha2-adrenoceptor down-regulates the activity of protein kinase A that results in the potentiation of the glycinergic inhibitory effects within the spinal dorsal horn.