Noradrenaline Uptake Mechanisms in Human Atrium

: The 3H-amine uptake and accumulation in vitro in human and rat heart tissue was compared. The equilibration and clearance of 3H-sorbitol was the same in both species, indicating similar diffusion conditions in the extracellular space. The uptake of 3H-metaraminol (3H-MA) in non-nervous tissue was measured by incubation at 0° or preincubation in desipramine, both procedures known to inhibit effectively the axonal ‘membrane pump’ uptake mechanism. The extraneuronal uptake in man and rat thus measured was similarly low. A high correlation was found between neuronal 3H-MA uptake and endogenous noradrenaline (NA) concentration measured in the same human atria, thus indicating the possibility of quantitatively estimating nerve density by measuring 3H-amine uptake. The neuronal uptake process for 3H-MA in heart tissue from both man and rat was found to obey Michaelis-Menten kinetics, whereas the affinity for the uptake sites was somewhat higher in the rat. Reserpine caused a reduced accumulation of 3H-NA in both species, which could be counteracted by the monoamine oxidase inhibitor, nialamide. The spontaneous release of 3H-NA previously taken up and accumulated was increased by reserpine in heart tissue of both man and rat. Pre-incubation in 6-hydroxydopamine led to a reduced uptake of 3H-MA, which was more pronounced in rat heart slices. The effect of certain drugs, known to affect monoamine uptake-storage mechanisms, on the 3H-MA uptake in heart slices from man and rat were studied. All the drugs investigated displayed a concentration dependent inhibition of the 3H-MA uptake. The order of inhibition potency was desipramine > protriptyline > imipramine > chlorpromazine > chlorimipramine. All the drugs studied induced a more marked uptake inhibition in human than in rat heart tissue. The adrenergic nerves of human and rat heart thus showed qualitative similarities regarding uptake and storage mechanisms, but some quantitative differences were found, e. g. a higher resistance to the neurotoxic effect of 6-hydroxydopamine and a more easily blocked ‘membrane pump’ by certain uptake blocking drugs in the human heart. It is suggested that these differences might be due to a less efficient ‘membrane pump’ in human adrenergic nerves.