title: Effect of inhibition of MAO and COMT on intrarenal dopamine and serotonin and on renal function.
abstract: The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol-O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 +/- 0.38 to 8.03 +/- 1.83 pg/min (n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 +/- 0. 18 to 1.57 +/- 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 +/- 0.70 to 8.68 +/- 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 +/- 0.16 to 2.76 +/- 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 +/- 2.00 to 9.82 +/- 1.62 micromol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 +/- 0.59 to 8.40 +/- 1.61 micromol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.
authors: Departments of Medicine and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
authors: Y
authors: Y
authors: Wang
authors: T J
authors: TJ
authors: Berndt
authors: J M
authors: JM
authors: Gross
authors: M A
authors: MA
authors: Peterson
authors: M J
authors: MJ
authors: So
authors: F G
authors: FG
authors: Knox
mesh_terms: D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004298:Dopamine / Q000032:analysis / Q000652:urine*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000652:urine*; D012964:Sodium / Q000378:metabolism
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010710:Phosphates; D012701:Serotonin; D012964:Sodium; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine