Supersensitivity to catecholamines after impairment of extraneuronal uptake or catechol-O-methyl transferase.
In cat papillary muscle and nictitating membrane block of extraneuronal catechol-O-methyl transferase (COMT) by 3',4'-dihydroxy-alpha-methyl propiophenone (U-0521) or of extraneuronal uptake by hydrocortisone causes supersensitivity to catecholamines whenever the experimental conditions result in a high sensitivity of the organ to catecholamines. After block of monoamine oxidase the extraneuronal O-methylation of (-)-[3H]norepinephrine by the isolated nictiating membrane is due to two O-methylating systems (Km and Vmax: 7.5 muM and 0.73 nmoles - g-1 - min-1, and 131 muM and 8.5 nmoles - g-1 - min-1, respectively). Hydrocortisone (28 muM) blocked the activity of the high affinity system without affecting the low affinity system. Apparently, there exists an extraneuronal compartment of high affinity that has a hydrocortisone-sensitive uptake mechnism; this compartment influences the concentration of catecholamines below the Km of this compartment. Supersensitivity ensues when either uptake or enzyme is blocked. Since the sensitivity effects of U-0521 and hydrocortisone are not additive, the high affinity compartment must a) metabolize most of the catecholamine transported into the compartment, and b) have a limited storage capacity for catecholamines after block of COMT.
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002415:Cats; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009541:Nictitating Membrane / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D011956:Receptors, Cell Surface
D008996:Monoamine Oxidase Inhibitors; D011956:Receptors, Cell Surface; D009647:Normetanephrine; D002394:Catechol O-Methyltransferase; D006854:Hydrocortisone; D009638:Norepinephrine