Development of transsynaptic regulation of adrenal enkephalin.

Transsynaptic activity differentially regulates biosynthesis of sympathoadrenal catecholamines and co-localized opiate peptides in the rat. We determined whether similar mechanisms were operative during development. Adrenal Leu-enkephalin (LEU), was first detected at E16.5, then increased 5-fold during maturation from birth to adulthood while adrenal weight increased 10-fold. Since medullary cells do not divide after the first postnatal week, this represents a specific maturational increase in LEU content per chromaffin cell. In adult medullae, decreasing transsynaptic activity through adrenal denervation or explantation results in a 30-50-fold increase in LEU. In contrast, LEU levels in denervated or explanted medullae from neonatal rats (less than or equal to 10 days) do not. Prolonged denervation (day 5-21) prevented even the normal maturational increase in LEU. However, depolarizing medullae with KCl lowered LEU levels at all ages tested with an increased magnitude of effect after 10 days postnatal age. Specific deficits in signal-transduction mechanisms or immaturity of opiate biosynthetic pathways may account for these observations. Thus, during development, adrenal opiate peptides are not under transsynaptic control yet require presynaptic terminals to mature normally. Therefore, like catecholamines, co-localized adrenal opiate peptides require presynaptic regulatory signals to achieve normal development and function.