Choline+: a substrate of the neuronal noradrenaline carrier in the rat vas deferens.
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. Choline+ (20 and 40 mmol/l) competitively inhibited the neuronal uptake of 3H-noradrenaline. From the choline+-induced changes in the apparent Km for 3H-noradrenaline transport, a Ki of 35 mmol/l was obtained. 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 mumol/l desipramine, indicating that choline+ is capable of eliciting "accelerative exchange diffusion". Choline+ (40 mmol/l) and (-)noradrenaline (4.5 mumol/l) (i.e., concentrations about equivalent to the Ki and Km for choline+ and (-)noradrenaline, respectively) produced virtually identical increases in the neuronal efflux of 3H-noradrenaline. Choline+ (3-300 mmol/l) inhibited the specific binding of 3H-desipramine to plasma membranes derived from cultured rat phaeochromocytoma (PC-12) cells. The Ki for this interaction was 48 mmol/l. 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.
D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D002794:Choline / Q000494:pharmacology*; D003891:Desipramine / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D012964:Sodium / Q000502:physiology; D014649:Vas Deferens / Q000378:metabolism
D002352:Carrier Proteins; D014179:Neurotransmitter Uptake Inhibitors; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C036079:desipramine receptor; D012964:Sodium; D002794:Choline; D003891:Desipramine; D009638:Norepinephrine