Noradrenaline overflow

As far as man is concerned, a presynaptic inhibition of the noradrenaline release by H3 receptors was only studied in the isolated human saphenous vein In this tissue, these receptors, similarly to a2-adrenoceptors, decrease the 3H-noradrenaline overflow elicited by electrical field stimulation (Molderings et al., 1992). Therefore, the role of histamine H3-receptors in the global control of the blood pressure in humans cannot be stated at present. 

Smit, J., Coppes, R.P., van Tintelen, E.J.J., Roffel, A.F., Zaagsma, J., 1997. Prejunctional histamine H3-receptors inhibit electrically evoked endogenous noradrenaline overflow in the portal vein of freely moving rats. Naunyn-Schmiedeberg s Arch. Pharmacol. 355, 256-260. 

Enero MA, Langer SZ, Rothlin RP, Stefano FJ. Role of the a-adrenoceptor in regulating noradrenaline overflow by nerve stimulation. Br J Pharmacol 1972 44 672-688. 

Many early studies of transmitter release depended on measuring its concentration in the effluent of a stimulated, perfused nerve/end-organ preparation. This technique is still widely used to study drug-induced changes in noradrenaline release from sympathetic neurons and the adrenal medulla. However, it is important to realise that the concentration of transmitter will represent only that proportion of transmitter which escapes into the perfusate ( overflow ) (Fig. 4.2). Monoamines, for instance, are rapidly sequestered by uptake into neuronal and non-neuronal tissue whereas other transmitters, such as acetylcholine, are metabolised extensively within the synapse. Because of these local clearance mechanisms, the amount of transmitter which overflows into the perfusate will depend not only on the frequency of nerve stimulation (i.e. release rate) but also on the dimensions of the synaptic cleft and the density of innervation. 

Effects of adenine nucleotides on neurotransmitter release were first observed at peripheral cholinergic synapses, where ATP, ADP, and adenosine were equipo-tent in inhibiting transmission (Ribeiro and Walker 1975 Su 1983). ATP also inhibited electrically evoked overflow of acetylcholine (Akasu et al. 1982 Silinsky and Ginsborg 1983) and noradrenaline (Clanachan et al. 1977 Enero and Saidman... 

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