Fig. 8

Schematic representation of the catecholaminergic pathway in RASFs. 1. Synthesis: RASF are able to synthesize DA, NE and EPI. This needs the participation of the enzymes TH, DDC, DBH and PNMT. 2. Storage: Vesicles are able to store catecholamines by transport through VMAT1 and VMAT2. 3. Release: Catecholamines can be released to the extracellular space by exocytosis and invoke downstream reactions via DRs and ADRs in an autocrine and paracrine fashion. Released catecholamines are able to ligate receptors (ADRs and DRs) and foster or inhibit secretion of IL-6. 4. Reuptake: Exogenous catecholamines are taken up through DAT or NET and repacked into vesicles or are degraded. 5. Degradation: MAO-A, MAO-B and COMT catalyze the degradation of excess catecholamines and thereby produce the metabolites DOPAC and HVA. (DA, dopamine; NE, norepinephrine; EPI, epinephrine; TH, tyrosine hydroxylase; DDC, DOPA decarboxylase; DBH, dopamine-beta-hydroxylase; PNMT, phenylethanolamine N-methyltransferase; VMAT1/2, vesicular monoamine transporter 1/2; DRs, dopamine receptors; ADRs, adrenergic receptors; DAT, dopamine transporter; NET, norepinephrine transporter; MAO-A/B, monoamine oxidase-A/B; COMT, catechol-O-methyltransferase; DOPAC, dihydroxy-phenyl acetic acid; HVA, homovanillic acid; IL-6, interleukin-6)