Adrenomedullary Secretion of DOPA, Catecholamines, Catechol Metabolites, and Neuropeptides

Abstract

Catecholamines and their metabolites have been proposed as markers of sympathetic nervous system stimulation. However, the adrenal medulla is a rich source of catecholamines and catecholamine metabolites and may play a significant role in plasma levels of these compounds. In addition to adrenal catecholamine metabolite efflux, the role of the catecholamine precursor 3,4‐dihydroxyphenylalanine (DOPA) has not been fully 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 during unstimulated conditions was epinephrine ≫ norepinephrine > 3,4‐dihydroxyphenylglycol > metanephrine > normetanephrine > dopamine > 3,4‐dihydroxyphenylacetic acid > 3‐methoxy‐4‐hydroxyphenylglycol ≥ DOPA ≫ [Met]enkephalin ≫ neuropeptide Y. Effluxes of analytes were not affected by cocaine and the ratios of catecholamines to metabolites increased dramatically with carbachol stimulation, consistent with negligible reuptake into adrenal cells. Thus, most of the 3,4‐dihydroxyphenylglycol is expected to be derived from epinephrine and norepinephrine subsequent to translocation from chromaffin vesicles into the cytosol. The efflux of DOPA increased dramatically during stimulation with 30 µM carbachol in a calcium‐dependent manner. Efflux of DOPA during the initial stabilization period of the perfusion preparation declined exponentially, in parallel with the effluxes of the catecholamines and neuropeptides but not with metabolites. Evoked release of DOPA was Ca2+‐dependent. These data suggest that DOPA can be stored and released exocytotically from chromaffin granules.

Catecholamines—Crafty Weapons in the Inflammatory Arsenal of Immune/Inflammatory Cells or Opening Pandora’s Box?

“…But, the question remains: how significant is the relative abundance of immune cell-derived catecholamines in comparison to the main catecholamineproducing organ, the adrenal medulla or presynaptic neurons? The adrenomedullary baseline production of epinephrine and norepinephrine in rodents is about 730pg/mL/min and 102pg/mL/min, respectively (26). In a recent study, 10 7 rat neutrophils produced about 100pg/mL and 20pg/mL while 10 7 rat macrophages released nearly 375pg/mL of epinephrine and 50pg/mL of norepinephrine when stimulated with 50ng/mL LPS (11).…”

l-DOPA and Its Receptor GPR143: Implications for Pathogenesis and Therapy in Parkinson’s Disease

“…Immunoprecipitation assay also revealed that the interaction between GPR143 and α 1B AR was enhanced by l -DOPA. Importantly, the enhancement was observed at a concentration comparable to those of plasma l -DOPA (10–20 nM) (Chritton et al, 1997; Goldstein et al, 2003; Masukawa et al, 2017). GPR143, when functionally coupled with α1 B AR, may have significantly more affinity for l -DOPA than when not forming heteromers with α1 B AR (Masukawa et al, 2017).…”

Simultaneous monitoring of monoamines, amino acids, nucleotides and neuropeptides by liquid chromatography-tandem mass spectrometry and its application to neurosecretion in bovine chromaffin cells

“…Although there are a large number of reports about determination of neurotransmitters in neuronal samples, however there is no method to assay all 14 compounds simultaneously in BCC samples. The secretion of dihydroxyphenylalanine, catecholamines, catecholamine metabolites and neuropeptides in adrenal chromaffin cells has been determined using HPLC with electrochemical detection . NA, AD and DA levels have also been determined using electrochemical detection, and NA, AD, DA and 5‐HT have been studied using HPLC‐MS in BCCs .…”