ISSN:
1432-1912
Keywords:
Hydrocortisone
;
Catecholamines
;
Postjunctional Supersensitivity
;
Extraneuronal COMT
;
Nictitating Membrane
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary On the isolated nictitating membrane of the cat the supersensitivity to catecholamines induced by hydrocortisone was compared with the ability of hydrocortisone to block the extraneuronal uptake and metabolism of catecholamines. 1. Supersensitivity to catecholamines was induced by hydrocortisone whenever the ED50 for the catecholamine (in the absence of hydrocortisone) was 10 μM or less. 2. The degree of hydrocortisone-induced supersensitivity was (-)-noradrenaline 〉 (-)-adrenaline 〉 (±)-isoprenaline; while 28 μM hydrocortisone sufficed to induce supersensitivity to noradrenaline and adrenaline, 280 μM were required for inducement of supersensitivity to isoprenaline. 3. Hydrocortisone had no potentiating effects after block of COMT (by 0.1 mM U-0521). 4. Hydrocortisone failed to affect the sensitivity to amines which are not substrates of COMT and also to indirectly acting sympathomimetic amines (tyramine, mephentermine). 5. The sensitivity experiments are consistent with the existence of a quickly equilibrating, extraneuronal O-methylating compartment with high affinity for catecholamines; it has a saturable, hydrocortisone-sensitive uptake mechanism and little or no capacity for storage of unchanged catecholamine. This postulated compartment influences the concentration of catecholamines in the biophase whenever the concentration of the catecholamine is below the K m of the compartment. 6. When COMT was blocked, hydrocortisone inhibited the distribution of 3H-(-)-noradrenaline into a quickly equilibrating extraneuronal compartment of small size. 7. In intact smooth muscles the extraneuronal O-methylation of 3H-(-)-noradrenaline and 3H-(±)-isoprenaline was carried out by two metabolizing compartments. One of these compartments had a high, the other a low affinity for catecholamines (apparent K m 7.5–12.8 and 131–201 μM, respectively). 8. Hydrocortisone inhibited the O-methylation of catecholamines by the high affinity compartment; an apparent non-competitive type of inhibition was obtained against (-)-normadrenaline and (±)-isoprenaline as substrates. 9. The biochemical experiments demonstrate the existence of an extraneuronal, saturable, hydrocortisone-sensitive O-methylating compartment with high affinity for catecholamines; this compartment equilibrates quickly with the concentration of the catecholamine in the medium and has little or no ability to accumulate unchanged catecholamines. 10. The biochemical results are in full agreement with the results from sensitivity studies.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00499103
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