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.
Lang
Bing
B
Department of Anatomy, The Fourth Military Medical University, Xi'an, 710032, PR China.
Li
Hui
H
Kang
Jie-Fang
JF
Li
Yun-Qing
YQ
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D009761:Nystatin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013449:Sulfonamides; D015016:Yohimbine / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; D018341:Receptors, Adrenergic, alpha-2; D013449:Sulfonamides; D009761:Nystatin; D015016:Yohimbine; C016299:chelerythrine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003000:Clonidine; D005998:Glycine; D009638:Norepinephrine