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A wide variety of glands are known to be under nervous control and are stimulated to secrete by neurohumours such as acetylcholine (ACh) and the catecholamines, but little is known of the way in which these neurohumours evoke secretion. It has recently been suggested that ACh stimulates the adrenal medulla by causing the chromaffin cells to take up calcium, and that the appearance of free calcium in the cells then elicits the secretory response. This idea that calcium is a vital link in the process of 'stimulus-secretion coupling' at the adrenal gland arose mainly from experiments showing that catecholamine secretion varies with extracellular calcium concentration over a wide range and that calcium itself is a secretogogue in conditions known to lead to increased permeability of cell membranes (Douglas & Rubin, 1961); it has gained support from the finding that ACh greatly increases 45Ca uptake by the adrenal medulla (Douglas & Poisner, 1961, 1962 a).The question obviously arises whether the role of calcium at the adrenal medulla is unique or whether calcium may also be intimately involved in other secretory processes, particularly those which are likewise initiated by ACh. Among the many glands responding to ACh the adrenal medulla is, of course, exceptional: it is an endocrine gland and its secretory chromaffin cells are derived from the neural crest and are thus related to neurones; moreover, it secretes catecholamines, whereas the secretions of the cholinoceptive exocrine glands consist chiefly of water, electrolytes and protein; and, finally, the ACh 'receptors' of the chromaffin cells are nicotinic rather than muscarinic in type. In spite of these differences, there are certain similarities between the above two types of glands, which suggest the possibility of a common secretory mechanism. Thus the secretion of catecholamines by the chromaffin cells and the secretion of protein by exocrine cells such as the pancreas or salivary glands have certain morphological features in common. In each instance the secretory product is * Post-Doctoral Fellow, United States Public Health Service.

We have recently described experiments on the neurohypophysis of the rat designed to reveal something of the events which occur when the neurosecretory terminals are stimulated and which lead to the extrusion of their stores of hormone (Douglas, 1963;Douglas & Poisner, 1963a, 1964. The experiments indicated that this train of events, which we refer to as 'stimulus-secretion coupling', involves depolarization followed by some calcium-dependent link. Thus vasopressin was released when the isolated neurohypophysis was stimulated electrically or was exposed to excess potassium; the stimulant effect of excess potassium varied with the extracellular calcium concentration over a wide range and was inhibited by magnesium; and, finally, the introduction of calcium was itself sufficient to evoke vasopressin release when the terminals were exposed to excess potassium. These findings led us to propose that 'stimulus-secretion coupling' in the neurohypophysis involves the following steps: first, the arrival of impulses propagated down the hypothalamo-hypophysial tract; second, depolarization of the neurosecretory terminals; and, third, an increased uptake of calcium. In this view the appearance of an excess of calcium somewhere in the neurosecretory terminals is the factor which sets in motion the process of extrusion of the posterior pituitary hormones.The present study was undertaken to obtain information on calcium movement in the neurohypophysis under the same experimental conditions. METHODSPreparation. The experiments were carried out on neurohypophyses from male rats weighing close to 140 g. The glands were removed and prepared for incubation as described previously (Douglas, 1963;Douglas & Poisner, 1964) except that the cut made along the sagittal plane to facilitate diffusion was incomplete to allow the individual glands to be recovered at the end of the experiment for measurement of radioactivity.Incubation media. The principal incubation medium was a modified 'Locke's solution' of the following composition (mm): NaCl, 154; KCI, 5-6; NaHCO3, 6-0; CaCl2, 2*2; MgC1,2 1-0; glucose 10-0. Several variations of this solution were used which had, for example,