Presynaptically acting catecholamines bind to alpha 2-adrenoceptors labelled by 3H-clonidine

It is known that certain catecholamine congeners can decelerate the heart rate by inhibiting the prejunctional sympathetic neurones to the atrium. The present study was done to determine whether this presynaptic action might be associated with either dopamine receptors or alpha-adrenergic receptors. The effects of 10 catecholamine congeners wee tested on the specific binding of 0.2 nM 3H-WB-4101 and 0.2 nM 3H-clonidine to calf frontal cortex homogenates, and that of 2 nM 3H-apomorphine to calf caudate nucleus homogenates. The drugs tested were apomorphine, the aminotetralin M-7, 3 dialkylated dopamine congeners, and 5 congeners of octahydrobenzo(f)-quinoline. The IC50 values (concentrations for 50% inhibition of binding) ranged from 400 to 28,000 nM for 3H-WB-4101, from 3 to 270 nM for 3H-apomorphine, and from 9 to 1000 nM for 3H-clonidine. Only the IC50 values for 3H-clonidine binding correlated with the in vitro IC50 values for inhibiting atrial acceleration (data from Long et al., 1975, 1979). These findings suggest that 3H-clonidine appears to bind to the same site in brain (alpha 2-adrenoceptor) on which catecholaminergic drugs act to produce cardiodeceleration.