Cyclic AMP regulates substance P expression in developing and mature spinal sensory neurons

The tachykinin, substance P, has long been associated with transmission of noxious stimuli. However, relatively little is known about signal transduct ion pathways subserving peptidergic regulation in sensory neurons. To inves tigate whether cyclic AMP (cAMP) could be a potential second messenger subs erving substance P expression, dorsal root ganglion neurons were grown in c ulture in the presence of agents that increase content of cAMP, In developi ng neurons, forskolin increased substance P content and survival almost thr eefold. Anti-nerve growth factor (NGF) blocked the effect of NGF but not fo rskolin, suggesting that increased cAMP acts directly and not via increased secretion of NGF from Schwann cells and fibroblasts. In adult neurons, whi ch do not require supplemental trophic factors for survival, NGF and forsko lin had similar effects on substance P levels. Neither agent had any effect on somatostatin content of either developing or mature sensory neurons. 8- bromo cAMP and isobutyl methylxanthine duplicated the action of forskolin, Further, all three agents increased expression of preprotachykinin mRNA. Fo rskolin appeared to increase both total and neuron-specific expression of m essage as well as the number of neurons expressing mRNA. Our results sugges t that cAMP directly regulates substance P content in sensory neurons from adult and neonatal rats. J. Neurosci. Res, 59: 624-631, 2000, Published 200 0 Wiley-Liss, Inc.dagger