Characteristics of the cocaine-sensitive accumulation and O-methylation of 3H-(-)-noradrenaline by rabbit endometrium.
1. The extraneuronal uptake and O-methylation of 2,5,6 3H-(-)-noradrenaline was studied in segments of uterine endometrium from rabbits pretreated with 17 beta-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 Km of 78 mumol/l and a Vmax of 5.4 nmol/g min. Uptake was inhibited by low Na+, and by potential substrates in the order dopamine greater than (-)adrenaline greater than (-)isoprenaline = 5-hydroxytryptamine. 3. Following uptake at 1.2 mumol/l, 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 mumol/l 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 mumol/l and a Vmax of 0.9 nmol/g X min. The formation was inhibited by the neuronal uptake inhibitors, desipramine 3 mumol/l and metaraminol 100 mumol/l (each by 80%), but was unaffected by the extraneuronal uptake inhibitor, NMN 100 mumol/l, and by oxytetracycline 100 mumol/l and methoxamine 10 mumol/l. 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Kennedy
J A
JA
Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia.
de la Lande
I S
IS
D000818:Animals; D001692:Biological Transport; D003042:Cocaine / Q000494:pharmacology*; D004717:Endometrium / Q000294:innervation / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008745:Methylation; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000096:biosynthesis; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology
D009647:Normetanephrine; D012964:Sodium; D003042:Cocaine; D006854:Hydrocortisone; D009638:Norepinephrine