�ber den Angriffspunkt der indirekten Wirkung sympathicomimetischer Amine

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

“…Whether it is the sucrose, or the lack of sodium and potassium, which is responsible for the release is uncertain, but the latter possibility is suggested by the fact that sucrose containing potassium 5-6 mM was much less effective. It is known that in pure sucrose the catecholamine granules isolated from the adrenal medullary cells tend to lose, their amine content (Hillarp, 1958;Schumann & Weigmann, 1960), but this effect is rather small at the temperatures at which we worked, and moreover it seems improbable that significant quantities of sucrose penetrate the medullary cells. The effect of isosmotie sucrose on the whole gland seems most probably to be a membrane phenomenon.…”

“…the motor end-plate, del Castillo & Katz, 1956) it appears to be confined to the membrane, probably its outer surface, and to involve the production of some increase in membrane permeability to common species of ions. There is, moreover, evidence that ACh does not act directly on the intracellular 52 CALCIUM AND ADRENAL MEDULLARY SECRETION 53 stores of catecholamines (the adrenal medullary granules) to cause release of catecholamines (Blaschko, Hagen & Welch, 1955;Schumann & Weigmann, 1960). If ACh acts on medullary cells to increase their permeability to calcium, an inward movement of calcium ions would be expected for the reasons we have just given.…”

Differential Effects of D 600 on Release of Catecholamines by Acetylcholine, Histamine, Tyramine and by Cyclic AMP from Canine Adrenal Medulla.

“…Indirectly acting sympathomimetic amines including tyramine are capable of releasing CA from bovine adrenal medullary granules in the absence of extracellular Ca2+ (5,6), and the displacement of CA by these amines from the storage site in the granules has been suggested as a release mechanism (6,21). Thus, the apparent requirement of the entry of Ca2+ for release of CA from the intact adrenal medulla by tyramine should be explained.…”

“…Acetylcholine (ACh), the physiological secretagogue of the adrenal medulla (1,2), and histamine, serotonin, angiotensin and bradykinin (3) require the presence of extracellular Ca2+ to release CA from there. Sympathomimetic amines such as tyramine have also been reported to require extracellular Ca2+ for release of CA from the perfused adrenal medulla (4), although these amines are capable of releasing CA from isolated medullary granules in the absence of environmental Ca2+ (5,6). Adenosine 3',5'-cyclic monophosphate (cyclic AMP), the implication of which is suggested in several secretory processes, has been shown to release CA from the perfused adrenal medulla in the absence of extracellular Ca2+ (7), whereas Jaanus and Rubin (8) failed to demonstrate the release of CA from there by cyclic AMP.…”

The Responses to Tyramine of the Normal and Denervated Nictitating Membrane of the Cat: Analysis of the Mechanisms and Sites of Action

“…Experiments published in the last two years have supplied direct proof for such an effect in vivo as well as in vitro (von Euler & Lishajko, 1960;Schumann & Weigmann, 1960;Lockett & Eakins, 1960;Schumann & Philippu, 1961;Lindmar & Muscholl, 1961;Carlsson & Hillarp, 1961;Cession-Fossion, 1962;Potter, Axelrod & Kopin, 1962;Chidsey, Harrison & Braunwald, 1962 ;Weiner, Draskoczy & Burack, 1962). Further evidence for this mode of action is provided by the fact that the sympathomimetic effect of tyramine on different effector organs (for example, arteries, heart, spleen, nictitating membrane and iris) can be reduced either by depleting stores of catechol amine (for example, by chronic denervation, treatment with reserpine or by tyramine itself) or by drugs (such as cocaine, guanethidine, bretylium and imipramine) which block the access of tyramine to catechol amine stores or to cells containing these stores (Schaeppi, 1960;Lindmar & Muscholl, 1961;Legic & Varagic, 1961;Axelrod, Gordon, Hertting, Kopin & Potter, 1962).…”