The postnatal development of norepinephrine-stimulated cyclic AMP accumulation in rat spinal cord

Norepinephrine (NE) stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation in regional spinal cord and cortical tissue slices from postnatal rats demonstrated distinct developmental patterns. NE-concentration-response studies using a 10-min incubation period demonstrated minimal NE-stimulated cyclic AMP accumulation in whole spinal cord at PD 1-5 with maximal sensitivity on PD 12. Thereafter, sensitivity decreased to adult values at PD 30. Sensitivity changes were reflected in alterations in maximal response only since NE EC50s all averaged 10(-6) M. This agrees with no change in calculated Kd for NE with increased Vmax to PD 12 and a reduction thereafter. Studies on regional spinal cord and cerebral cortical cyclic AMP accumulation indicated peak NE sensitivity in cervical and thoracic cord occurred at PD 10, in lumbar cord at PD 15, and in cerebral cortex at PD 20. The fact that inhibition of phosphodiesterase (PPDE) produced the same percentage alteration in peak accumulation in spinal cord slices regardless of postnatal age suggests that PPDE is not the primary determinant of the ontogenic changes. The results indicate that the postnatal development of spinal NE receptors may be reflected in an increase in the responsiveness of the cyclic AMP system to NE.