The estimation of adrenaline and allied substances in blood

Abstract

Much work has been devoted to the search for a really sensitive and specific method of detecting and estimating adrenaline and allied substances in blood. This search has gained importance in recent years because of the desire to identify the substances liberated by adrenergic nerves. These substances can only be expected to appear in very low concentrations, and sensitive and specific tests are needed for their study. This paper describes part of the search for such tests and is a continuation of the work of West (1947a, b) in this department.The most sensitive tests for adrenaline are pharmacological tests, but no single test is really specific by itself. A number of other sympathomimetic amines are known to have effects like those of adrenaline, but they can sometimes be distinguished by the method of parallel quantitative assays. If the adrenaline-equivalent of a solution is estimated quantitatively by several different methods, and the results differ significantly among themselves, adrenaline cannot be the only active substance in the solution. If the results agree among themselves, then the evidence supports the theory that the solution contains adrenaline, but its value depends on the use of pharmacological methods which vary independently in their sensitivity to drugs closely allied to adrenaline. If small changes in the molecule affect all the tests equally, then parallel quantitative assays are of little value. One of the objects of the present investigation was to discover a set of tests which would vary independently in their response to sympathomimetic amines, so that they could be used to distinguish these amines from one another.

The Effect on Respiration of Infusions of Adrenaline and Noradrenaline Into the Carotid and Vertebral Arteries in Man

“…The doses are expressed as weights of the salts. Adrenaline has been shown to remain stable in ascorbic acid saline for many hours (Gaddum, Peart, and Vogt, 1949).…”

The Role of the Spleen in the Adrenaline Reversal and the Theory of This Phenomenon

“…There is al.so evidence that in some cases adrenaline is even a more powerful vasoconstrictor than noradrenaline, e.g. for the vascular system of the rabbit's ear (Luduena et al, 1949;Burn and Hutcheon, li*49), for the renal vessels of dogs, cats and rabbits (Ahlquist, 1948;Burn aud Hutcheon, 1949;Gaddum, Peart and Vogt, 1949), and for the vessels of the frog (West, 1947). This is not unexpected, since adrenaline has also a stronger motor action on some other plain muscular structures like the retractor penis of dogs (Barger !ind Dale, 1910;Luduenu et al, 1949b), tlie dilator of the iris and the nictitating membrane of the cat (Greer et al, 1938;Acheson, 1940, Burn andHutcheon, 1949).…”

“…(b) Extracts of adrenergic neives contain a sympathomimetie substance which has the biological effects of noradrenaline (v. Euler, 1946aEuler, , d, 1948aBaeq and Fischer, 1947) ; (c) The same holds true for extracts of organs with sympathetic nerve snpply, sueh as the spleen, heart and blood vessels (v. Euler, 1946b, c;St-hniitterlow, 1948b;Raab and Lepeschkin, 1950); (d) the amount of noradrenaline-like substance in organ extracts is related to the sympathetic innervation; e.g. it decreases after degeneration of the nerve supply, and ia absent from the nerve-free placenta (v. Kuler, 1945;Schmitterlow, 1948b) ; (e) the blood coming from liver or spleen during stimulation of the corresponding sympathetic nerves also contains a substance with the biological properties of noradrenaline (Gaddum and Goodwin, 1947;Peart, 1949); (f) the vasoconstrictors in the hind legs or in the splanchnic area of the cat act most likely by liberation of noradrenaline (Folkow and Uvnas, 1948a;Folkow et al, 1948d).…”

“…Euler, 1948v. Euler, , 1949Schmitterlow, 1948b, Peart, 1949West, 1949). Bacq and Fischer have perhaps best summarized the facts by stating that the sympathetic transmitter may be a mixture of noradrenaline and adrenaline in variable proportions.…”

Effect of Chlorpromazine on Adrenaline Vasoconstriction in Man

“…were prepared by serial dilution with saline. The potency of the adrenaline was maintained by adding 0.1 mg. ascorbic acid to each pint of saline used in the infusions (Gaddum, Peart, and Vogt, 1949).The effect of chlorpromazine on the peripheral constriction caused by adrenaline was studied in two series of experiments. In the first of these the effect of intra-arterial chlorpromazine on the vasoconstriction produced by intra-arterial and by intravenous adrenaline was measured; this study also enabled the direct action of chlorpromazine alone on the calibre of the vessels to be assessed.…”