Dynorphins other than dynorphin A(1-17) lack spinal antianalgesic activity but do act on dynorphin A(1-17) receptors

JJ Rady, JM Fujimoto and LF Tseng

Research Service, Veterans Administration Medical Center, Milwaukee, Wisconsin.

In recent publications we have proposed that dynorphin (Dyn) A(1-17) functions as an antianalgesic modulator to oppose opioid-induced antinociception in mice. In the present experiments using the tail- flick response in mice, other Dyns [Dyn A(1-8), Dyn A(1-13), Dyn A(2- 17), Dyn B and alpha- and beta-neoendorphin] when administered intrathecally (i.t.) were shown not to have antianalgesic activity even at high doses (0.5-1 pmol). These Dyns, i.t., did not antagonize the antinociception produced by physostigmine administered i.c.v. or morphine given i.t. These Dyns lacked the intrinsic antianalgesic activity of Dyn A(1-17). However, they had affinity for Dyn A(1-17) receptors as shown in several ways. 1) The antagonism of physostigmine antinociception produced by Dyn A(1-17) given i.t. was reversed by these Dyns given together with Dyn A(1-17). 2) The effect of endogenously released Dyn A(1-17) was reversed. Administered i.c.v., clonidine simultaneously activates antinociceptive and antianalgesic systems [latter mediated spinally by Dyn A(1-17) release]. Thus, these Dyns given i.t. inhibited the action of endogenously released Dyn A(1- 17) and allowed the full manifestation of the antinociceptive action of clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 259, Issue 3, pp. 1073-1080, 12/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics

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