The occurrence of galanin (GAL) in the spinal cord and reports suggesting that it acts as an endogenous inhibitory spinal modulator in sensory/noxious transmission, have focused interest on its metabolism in the spinal cord. The metabolic half-lives and degradation patterns of GAL(1-29) and the high affinity N-terminal fragment GAL(1-16), were determined in isolated cerebrospinal fluid (CSF) from rats, and analysed by reverse phase HPLC. The half-lives for GAL(1-29) and GAL(1-16) in isolated rat CSF at 37 degrees C were 120 min and 60 min, respectively. The first degradation products which we could isolate and identify of GAL(1-16) were: GAL(3-16) and GAL(3-12) and for GAL(1-29): GAL(1-5) and GAL(1-4), all without affinity to spinal galanin receptors. Degradation studies of GAL(1-29) and GAL(1-16) in a spinal cord membrane preparation, in absence or presence of different protease inhibitors: E-64, pepstatin A, 3,4-DCI, bestatin, phosphoramidon, kelatorphan and thiorphan, or metal chelators: EDTA, EGTA and o-phenanthrolin, suggest that a phosphoramidon sensitive zinc-metalloprotease is mainly responsible for the degradation of GAL(1-29) and GAL(1-16), since both o-phenanthrolin (0.3 mM) and phosphoramidon (920 microM) substantially prolong their half-lives.