Effects of dynorphin A (1-17) on motor function and spinal intracellular messenger systems in rat.
The effect of intrathecal injection of dynorphin A (1-17) on second messenger systems of spinal cord relative to behavioral change in rats was studied. Dynorphin A (1-17) 5, 10 (20 nmol) caused dose-dependent flaccid paralysis of hindlimbs. Dynorphin A (1-17) 10, 20 nmol dose-dependently decreased spinal adenylate cyclase (AC) activity, cyclic AMP production, calmodulin (CaM) level and cyclic-nucleotide phosphodiesterase (PDE) activity 10 min after intrathecal injection. They recovered to a varying extent two hours later. Pretreatment with selective kappa-opioid receptor antagonist nor-BNI 30 nmol 10 min before dynorphin A (1-17) markedly antagonized the effects of dynorphin A (1-17) at 20 nmol on hindlimb paralysis and inhibition of intracellular second messengers. The L-type calcium channel blocker verapamil (100 nmol) also played a role in blocking dynorphin neurotoxicity. The NMDA receptor antagonist APV could partially or completely block dynorphin inhibition of CaM level and PDE activity without affecting paralysis and decrease of AC-cAMP level induced by dynorphin A (1-17) 10 min after intrathecal injection.
Zhang
Z
Z
Department of Pharmacology, Institute of Basic Medical Sciences, CAMS, Beijing.
Li
F
F
Ren
M
M
Liu
J
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004399:Dynorphins / Q000494:pharmacology*; D005260:Female; D007278:Injections, Spinal; D009043:Motor Activity / Q000187:drug effects; D009123:Muscle Hypotonia / Q000139:chemically induced / Q000378:metabolism; D010243:Paralysis / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D013116:Spinal Cord / Q000502:physiology*
D002147:Calmodulin; D004399:Dynorphins; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases