Isolated Neurohypophysial Nerve Endings, a Promising Tool to Study the Mechanism of Stimulus-Secretion Coupling

Abstract

Douglas and co-workers demonstrated in their pioneering work that depolarization of the plasma membrane and the presence of external calcium are two of the prerequisites in excitable cells for an increase in secretion to occur (Douglas and Rubin, 1963; Douglas and Poisner, 1964). They showed that activation of cholinergic receptors in the adrenal medulla or potassium-induced depolarization of the neurohypophysis gave rise to calcium uptake in these tissues. Consequently they hypothetised that catecholamine release and neurohypophysial hormone secretion are induced by an increase in the cytoplasmic calcium concentration. In the seventies, it was shown that the depolarization induced 45Ca2+ uptake and the release of hormones from the neural lobe could be inhibited by agents known to block calcium channels (Dreifuss et al., 1973). The picture which emerged from these results was that in the neural lobe the arrival of action potentials promotes the opening of voltage-sensitive calcium channels and this leads, due to the large calcium gradient across the membrane, to the entry of calcium. The resulting increase in the free cytoplasmic calcium concentration would then, by an unknown process, trigger exocytosis. Although the neural lobe is the material of choice for studying secretion per se, it suffers from certain disadvantages such as the presence of non-neuronal cells, of a tortuous extracellular space making the diffusion into or out of the tissue very slow, and of the presence of molecules in the extracellular space which prevent, because of their high affinity for lectin-like material, the use of the latter as label for the cell membrane.