Biological activities of two endogenously occuring N-terminally extended forms of galanin in the rat spinal cord

The occurrence of two N-terminally extended forms of galanin in the porcine adrenal medulla was reported earlier by Bersani et al. (1991). We have synthesized and examined the ability of these two extended forms of galanin, galanin-(-7-29) and galanin-(-9-29), to bind to galanin receptors in the rat dorsal spinal cord. The effect of intrathecal (i.t.) injection of these peptides on spinal flexor reflex excitability in decerebrate, spinalized, unanesthetized rats was also studied. Both galanin-(-7-29) and galanin-(-9-29) fully displaced specific 125I-monoido-[Tyr26]porcine galanin (125I-galanin) binding to membranes prepared from rat dorsal spinal cord, with IC50 values 0.13 and 0.14 microM, respectively. The metabolic half-lives in spinal cord membranes for galanin-(1-29), galanin-(-7-29) and galanin-(-9-29) were 117 +/- 17, 271 +/- 23 and 185 +/- 19 min, respectively. I.t. injection of galanin-(-7-29) and galanin-(-9-29) mimicked the biphasic facilitatory and inhibitory effect of i.t. galanin-(1-29) on flexor reflex excitability and antagonized C-fiber conditioning stimulus-induced spinal cord hyperexcitability, but with reduced potencies compared to galanin-(1-29). We suggest that the N-terminally extended forms of galanin act as endogenous ligands with low agonist activity.