Download Calcium and the Secretory Process by Ronald Rubin PDF

By Ronald Rubin

An huge, immense quantity of analysis attempt has been directed towards elucidating the mechanism in which ingredients are extruded from cells; and experiences were written and symposia held for you to systematize the plethora of proof made on hand. despite the fact that, the methods hired to check the secretory strategy were so different that it truly is tough, if no longer most unlikely, for one person or perhaps a staff of people to maintain abreast of all elements of the sector and to research them significantly. hence I undertook the writing of this quantity with loads of trepidation. In trying to find a few place to begin, I obviously regarded as my fundamental concentration the function of calcium within the secretory technique, which has occupied my study pursuits for the earlier thirteen years. yet in view that loads experimentation has been performed in this and similar themes over the last decade or , I felt it used to be nonetheless essential to visualize this enterprise from substitute ap­ proaches: (1) a extra normal one, which might hide the topic of calcium and the secretory strategy from a large point of view, yet after all no longer in nice element, and (2) a extra particular one, proscribing assurance to scrupulously outlined limits yet with entire research of constrained issues. the ultimate path undertaken seems to be to lie someplace among those extremes.

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These investigators ascribed the effects of calcium deprivation to a direct effect on the release reaction and not to an effect on impulse conduction, since they noted that calcium lack produced hyperexcitability of the neuronal elements although synaptic transmission was blocked. Katz and his associates (cf. Katz, 1958, 1969) have very productively employed the frog neuromuscular junction for studying transmitter release, despite the fact that acetylcholine is not measured directly. Using microelectrode techniques, they have demonstrated that the miniature end-plate potentials represent basic units (quanta) of transmitter activity and that the end-plate potential consists of a summation of such quanta.

32 2 Action of Calcium on the Secretory Process inhibits the secretory response to acetylcholine as well as to calcium. These results were compatible with the existing evidence concerning the mode of action of acetylcholine at other sites of cholinergic transmission where it was thought to act at the outer surface of the membrane to increase permeability. The calcium dependence of acetylcholine in the secretory response might be explained by a need for calcium in the binding to receptors on the chromaffin cells, but this possibility was mitigated not only by the ability of calcium itself to elicit secretion but also by the finding that calcium is required for catecholamine secretion elicited by excess potassium, which presumably acts by depolarizing the cell membrane in the absence of any known drug-receptor interaction.

Remember, now, this was 1960, and chemical methods for determining catecholamines were still being developed. Besides, much of Douglas's training had taken place in England, where, under the guidance of such stalwarts as Sir Henry Dale, Gaddum, and Feldberg, bioassay techniques had been developed for identifying and quantitating biological substances. So the rabbit aortic strip-the preparation of which, up to that time, Robert Furchgott (1960) had utilized so successfully for studying drug-receptor mechanisms-was employed to carry out the assay of the adrenal perfusate.

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