Choline⁺: A substrate of the neuronal noradrenaline carrier in the rat vas deferens

Summary

• 1. The effects of choline⁺ (10–40 mmol/l) on ³H-noradrenaline uptake by, and ³H-noradrenaline efflux from, noradrenergic neurones were studied in vasa deferentia of reserpine-pretreated rats at an external Na⁺ concentration of 100 mmol/l. Monoamine oxidase and catechol-O-methyltransferase were inhibited.

• 2. Choline⁺ (20 and 40 mmol/l) competitively inhibited the neuronal uptake of ³H-noradrenaline. From the choline⁺-induced changes in the apparent K_m for ³H-noradrenaline transport, a K_i of 35 mmol/l was obtained.

• 3. Choline⁺ (10, 20 and 40 mmol/l) accelerated the neuronal efflux of ³H-noradrenaline in a concentration-dependent manner. This acceleration of efflux was greatly reduced in the presence of 1 μmol/l desipramine, indicating that choline⁺ is capable of eliciting “accelerative exchange diffusion”.

• 4. Choline⁺ (40 mmol/l) and (−)noradrenaline (4.5 μmol/l) (i.e., concentrations about equivalent to the K_i and K_m for choline⁺ and (−)noradrenaline, respectively) produced virtually identical increases in the neuronal efflux of ³H-noradrenaline.

• 5. Choline⁺ (3–300 mmol/l) inhibited the specific binding of ³H-desipramine to plasma membranes derived from cultured rat phaeochromocytoma (PC-12) cells. The K_i for this interaction was 48 mmol/l.

• 6. This results suggest that choline⁺ acts as alternative substrate of the neuronal noradrenaline transport system and should, therefore, not be used in transport studies with noradrenaline as substitute for Na⁺ in Na⁺-deficient media.