Treatment with 6-hydroxydopamine and colchicine decreases nerve growth factor levels in sympathetic ganglia and increases them in the corresponding target tissues.

A two-site enzyme immunoassay was used to determine the nerve growth factor (NGF) contents of sympathetic ganglia and their corresponding target tissues in adult rats. The destruction of sympathetic nerve terminals by 6-hydroxydopamine (6-OHDA) and the blockade of axonal transport by colchicine resulted in a rapid increase in the NGF levels of sympathetically innervated organs and a rapid decrease in the sympathetic ganglia. NGF levels in heart atrium, heart ventricle, submandibular gland, and iris increased 2- to 4-fold 12 hr after injection of 6-OHDA, whereas the NGF contents of stellate and superior cervical ganglia dropped to a minimal level of 3 to 4% of control 24 hr after injection. Twelve hours after treatment with colchicine the NGF levels in sympathetically innervated organs increased 2- to 3-fold, whereas the NGF contents of sympathetic ganglia fell to one-third of control values. The half-lives of NGF in the superior cervical and stellate sympathetic ganglia were 4.5 and 4.8 hr, respectively, as determined by the decrease of NGF content after treatment with 6-OHDA. These results indicate that the synthesis of NGF is normally confined to the innervated target organs with no significant contribution of ganglionic cells. This is consistent with the concept that NGF acts as a retrograde messenger between target organs and innervating sympathetic neurons.