Spinal cord dynorphin precursor intermediates decline during late gestation.

This laboratory has previously reported that the maternal opioid analgesia associated with pregnancy and parturition is mediated, at least in part, by a maternal spinal cord dynorphin/kappa opioid system. This analgesia is accompanied by an increase in dynorphin peptides (1-17 and 1-8) in the lumbar spinal cord. Levels of trypsin-generated arginine6-leucine-enkephalin (Leu-Enk-Arg)-immunoreactive determinants were also determined and used to reflect the content of dynorphin precursor intermediates. In spinal tissue, the amount of dynorphin A (1-17) contained in the form of precursor is, at a minimum, 10-fold higher than the content of mature dynorphin A (1-17) or dynorphin (1-8). During gestational day 22, the content of dynorphin precursor is reduced significantly (approximately 50%). The decline in the magnitude of dynorphin precursor intermediates in the spinal cord of pregnant rats vastly exceeds the magnitude of increase in the content of dynorphin peptides (1-17 and 1-8). This difference can best be explained by postulating a corresponding increase in the rate of release of spinal cord dynorphin (1-17). It is suggested that enhanced processing of dynorphin precursor intermediates represents the initial biochemical level of adaptation of spinal dynorphin neurons to increased demands of pregnancy.