DUAL PATHWAYS REGULATE NEURITE OUTGROWTH IN ENTERIC GANGLIA

Primary cultures of guinea pig myenteric plexus ganglia were used to e xamine the ability of agents that activate adenylate cyclase or mimic intracellular adenosine 3',5'-cyclic monophosphate (cAMP) to stimulate morphological growth. Dose-dependent increases in neurite length and density were produced in enteric neuronal cultures by forskolin (212% of control), cholera toxin (356% of control), or the permeant cAMP ana logues 8-bromoadenosine 3',5'-cyclic monophosphate and dibutyryl cAMP. (R)-p-adenosine 3',5'-cyclic monophosphorothioate, an inhibitor of cA MP-dependent kinases, blocked the growth-promoting effects of cAMP ana logues but not of nerve growth factor (NGF). Activation of cAMP-depend ent signaling pathways also increased production of mRNA for alpha-tub ulin and microtubule-associated protein 2. Dual pathways, regulated by NGF and cAMP-dependent protein kinases, influence growth signaling in enteric ganglia.