[Effects of high dose of dynorphin on NMDA receptor and NOS activities in spinal cord of rats].
OBJECTIVE
To elucidate the effects of N-methyl-D-aspartate(NMDA) receptor and nitric oxide synthase (NOS) activity in dynorphin (Dyn)-induced spinal cord injury.


METHODS
The NMDA receptor activity was measured by radio-ligand of 3H-MK801. The constitutive and inducible NOS (cNOS and iNOS) activities were assayed by 3H-arginine conversion.


RESULTS
In ventral samples, both 3H-MK801 binding and cNOS activity increased at 0.5 h and persisted for 48 h while iNOS activity enhanced at 4 h after intratheacal injection (i.t.) Dyn A(1-17) at dose of 20 nmol/L. However, the 3H-MK801 binding activity reduced significantly from 4 h to 24 h and cNOS activity did not change at the same time in dorsal samples. 7-nitroindozol (7-NI) and aminoguanidine (AG) inhibited the effects of Dyn A(1-17) (20 nmol/L) on 3H-MK801 binding and NOS activities in ventral samples. N-nitro-L-arginine methyl ester (L-NAME) did not affect the elevation of Dyn A(1-17) on NOS activities but caused 3H-MK801 binding activity reduction in ventral samples.


CONCLUSIONS
NMDA-NOS pathway might play important role in Dyn spinal neurotoxicity. NOS inhibitors and Dyn might produce cooperative down-regulation on the function of NMDA-NOS pathway in dorsal cord.
Qiang
W
W
Department of Pharmacology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Sun
L
L
Hu
W
W
Zuo
P
P
Ren
M
M
Liu
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D004399:Dynorphins; D019001:Nitric Oxide Synthase