The role of calcium in the secretory response of the adrenal medulla to acetylcholine

Abstract

It is commonly believed that acetylcholine (ACh) is the physiological transmitter of sympathetic nerve impulses at the adrenal medulla. The reasons are the following: the sympathetic nerve fibres that innervate the adrenal medullary cells are developmental homologues of the preganglionic fibres elsewhere in the sympathetic nervous system which are known to be cholinergic; on stimulation of the adrenal nerves an acetylcholine-like substance is released from the adrenal gland (Feldberg, Minz & Tsudzimura, 1934); ACh is a powerful stimulant of adrenal medullary secretion; and finally, transmission at the adrenal medulla is affected by a variety of drugs in much the same way as these drugs affect transmission at the established sites of cholinergic transmission at sympathetic ganglionic synapses.The purpose of the present experiments was to study the mechanism by which ACh brings about adrenal medullary secretion and, as a first approach, to observe how the response of the gland to ACh might be influenced by changes in the ionic composition of the extracellular environment. Our experiments show that the excitant action of ACh on the adrenal medulla is dependent on the presence of calcium, and suggest that ACh evokes adrenal medullary secretion by causing calcium ions to penetrate the adrenal medullary cells.

Mitochondria and chromaffin cell function

“…Since Douglas and Rubin [21] showed, in1961, that Ca 2+ entry was the only requirement to trigger the acetylcholinemediated release of catecholamines from the adrenal gland, we have learned much about basic and molecular aspects of Ca 2+ signalling and exocytosis in chromaffin cells. …”

“…In addition, Ca 2+ triggering of adrenaline secretion from chromaffin cells has been used as a general model for stimulus-secretion coupling [20]. According to the initial formulation, stimulus promotes Ca 2+ entry, which increases the cytosolic Ca 2+ concentration ([Ca 2+ ] C ) and triggers exocytosis [20,21]. Later studies showed that the genesis of the [Ca 2+ ] C signal includes subtle nuances contributed by the intracellular Ca 2+ -handling organelles [5,8,24,25].…”

Fusion of secretory vesicles isolated from rat liver

“…In analogy with "electromechanical coupling" in muscle fibers for the chain of events between recognition of a stimulus and release of a secretory product, Douglas and Rubin [27] several years ago introduced the term "stimulus-secretion-coupling." In this process Ca z+ ions were believed to play an important role since Ca 2+ ions are required in the extracellular fluid to stimulate a secretory cell successfully [25,27,35,37,52].…”

“…In this process Ca z+ ions were believed to play an important role since Ca 2+ ions are required in the extracellular fluid to stimulate a secretory cell successfully [25,27,35,37,52]. Later from flux measurements in different systems it was concluded that an increase of intracellular Ca 2 + may be necessary for the transformation of the stimulus into release of secretory products [13,23,24,26,36,48,49].…”

Tumor promoters potentiate the adrenomedullary secretion induced by acetylcholine and excess K possibly by stimulating phorbol ester receptors.

“…Adrenal glands of the cats were retrogradely perfused at room temperature (25-28°C) through the adrenolumbar vein (DOUGLAS and RUBIN, 1961). Perfusion rate was kept constant (1 ml/min) by means of a peristaltic pump.…”