ADRENOMEDULLARY SECRETION OF DOPA, CATECHOLAMINES, CATECHOL METABOLITES, AND NEUROPEPTIDES

Catecholamines and their metabolites have been proposed as markers of sympathetic nervous system stimulation. However, the adrenal medulla i s a rich source of catecholamines and catecholamine metabolites and ma y play a significant role in plasma levels of these compounds, In addi tion to adrenal catecholamine metabolite efflux, the role of the catec holamine precursor 3,4-dihydroxyphenylalanine (DOPA) has not been full y evaluated. The simultaneous effluxes of catecholamines, metabolites, DOPA, and neuropeptides were measured in perfusates from isolated dog adrenals, The relative abundance of compounds detected consistently d uring unstimulated conditions was epinephrine much greater than norepi nephrine > 3,4-dihydroxyphenylglycol > metanephrine > normetanephrine > dopamine > 3,4-dihydroxyphenylacetic acid > 3-methoxy-4-hydroxypheny lglycol greater than or equal to DOPA much greater than [Met]enkephali n much greater than neuropeptide Y. Effluxes of analytes were not affe cted by cocaine and the ratios of catecholamines to metabolites increa sed dramatically with carbachol stimulation, consistent with negligibl e reuptake into adrenal cells. Thus, most of the 3,4-dihydroxyphenylgl ycol is expected to be derived from epinephrine and norepinephrine sub sequent to translocation from chromaffin vesicles into the cytosol. Th e efflux of DOPA increased dramatically during stimulation with 30 mu M carbachol in a calcium-dependent manner. Efflux of DOPA during the i nitial stabilization period of the perfusion preparation declined expo nentially, in parallel with the effluxes of the catecholamines and neu ropeptides but not with metabolites. Evoked release of DOPA was Ca2+-d ependent, These data suggest that DOPA can be stored and released exoc ytotically from chromaffin granules.