Co-release of enkephalin and catecholamines from cultured adrenal chromaffin cells

The opioid peptides Leu-enkephalin and Met-enkephalin are stored intraneuronally in the brain where they are thought to act as neurotransmitters and/or neuromodulators. Evidence for their release from nerve terminals has come from biochemical and pharmacological studies in vitro with brain tissue slices and synaptosomes. Enkephalins also exist in the peripheral nervous system in nerve cell bodies and axon terminals in the gastrointestinal tract, sympathetic ganglia and adrenal gland. In the adrenal gland, high levels of enkephalins are present both in axon terminals of the splanchnic nerve and in the adrenal medullary chromaffin cells where they are stored together with the catecholamines in the chromaffin granules. Stimulation of the adrenal gland in vivo or the perfused gland in vitro causes release of catecholamines and enkephalins into the adrenal vein. However, it is not clear whether the origin of the released enkephalins is the adrenal medullary chromaffin cells or the enkephalin-containing splanchnic nerve terminals that innervate the medulla. We now show that enkephalin and catecholamines are released together from primary cultures of bovine adrenal medullary chromaffin cells by nicotine in a Ca2+-dependent manner.