Characteristics of the cocaine-sensitive accumulation and O-methylation of 3H-(−)-noradrenaline by rabbit endometrium

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Abstract
1. The extraneuronal uptake and O-methylation of 2,5,6 3H-(−)-noradrenaline was studied in segments of uterine endometrium from rabbits pretreated with 17β-oestradiol and progesterone. 2. The uptake of 3H-noradrenaline was measured in MAO- and COMT-inhibited tissues and obeyed Michaelis-Menten kinetics with an apparent K m of 78 μmol/1 and a V max of 5.4 nmol/g min. Uptake was inhibited by low Na+ and by potential substrates in the order dopamine > (−)adrenaline > (−)isoprenaline = 5-hydroxytryptamine. 3. Following uptake at 1.2 μmol/1, efflux of 3H-noradrenaline was slow and appeared to be from two compartments, of which the first (I) had a t1/2 of 53 min and a capacity of 1.8 nmol/g. The presence of the second compartment (II) was inferred from the tissue content of 3H after 60 min of efflux, which was 3–4 times greater than predicted if the 3H was present in compartment I only. Following incubation with 3H-noradrenaline in the presence of cocaine 30 μmol/1 the 3H efflux was rapid and the combined capacities of compartments I and II were greatly decreased. 4. 3H-NMN formation, measured in MAO-inhibited tissues, obeyed Michaelis-Menten kinetics with a half-saturating outside concentration of 12 μmol/1 and a V max of 0.9 nmol/g · min. The formation was inhibited by the neuronal uptake inhibitors, desipramine 3 μmol/1 and metaraminol 100 μmol/1 (each by 80%), but was unaffected by the extraneuronal uptake inhibitor, NMN 100 μmol/1, and by oxytetracycline 100 μmol/1 and methoxamine 10 μmol/1. 5. 3H-NMN formation was inhibited to a small extent (by 30%) by hydrocortisone in a concentration which inhibited 3H-NMN formation in the myometrium by 84%. 6. It is concluded that the extraneuronal uptake of exogenous noradrenaline in the endometrium (a) resembles uptake in sympathetic nerves in its sensitivities to sodium ions and uptake inhibitors, and (b) resembles corticosteroid-sensitive extraneuronal uptake in that it has a low affinity for noradrenaline, but is linked with O-methylation in a fashion which renders uptake and O-methylation a relatively high-affinity, low-capacity system for removing noradrenaline.

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