Identification of an Isoprenaline‐like Substance in Extracts of Adrenal Glands

Abstract

A sympathomimetic amine, not hitherto described as naturally occurring, was unexpectedly encountered in an experiment in which the adrenaline and noradrenaline, in saline extracts of cat adrenal glands, were being separated chromatographically.In this experiment a chromatogram, made from an aliquot of extract corresponding to just less than one-third of a cat gland, was oxidized, by spraying with a solution of potassium ferricyanide, to convert any primary or secondary catechol amines to the corresponding adrenochromes. Adrenaline and noradrenaline then appeared as red and pink spots respectively, and were identified by means of their RF values. There was, however, an additional very pale pink spot (third amine), with an RF value of approximately 0.7, lying ahead of the adrenaline area from which it was separated by a negative horizontal band of paper. Corresponding bands from another, similar, and adjacent chromatogram were therefore eluted and prepared for biological testing. The eluate from the negative zone separating the adrenaline area from that of the third amine was pharmacologically inert, whereas that from the zone of the third amine was highly active. lforeover, the type of activity encountered in the latter zone differed markedly from that obtained from the adrenaline and noradrenaline areas. The third amine, like adrenaline and unlike noradrenaline, strongly antagonized the action of acetylcholine on the rat uterus. However, when doses of adrenaline and of third amine eluates, which had proved equally active on the rat uterus, were injected intravenously into a cat under chloralose, the adrenaline eluate raised the mean arterial pressure and caused contraction of the nictitating membrane as expected, but the eluate of third amine lowered the blood pressure, caused tachycardia, and was without action on the nictitating membrane.The results of a further investigation of this third amine are presented here in three sections. The first section is concerned with the great similarity between the third amine and isoprenaline. The second section deals with the presence or absence of the third amine in the adrenal glands of various species. Finally, the properties and actions of the third amine have been contrasted with those of lactyladrenaline and lactylnoradrenaline, because these two compounds are known sometimes to arise as artifacts in extracts of adrenal glands. Lactyladrenaline was first isolated by Kendall (1932) and was studied, together with lactylnoradrenaline, by Crawford (1951). Work by Serlin and Goldenburg (1953) on the instability of synthetic noradrenaline in acid ethanol indicated that these so-called lactyl derivatives may prove to be ethers. Their hypothesis has not been investigated; the terms lactyladrenaline and lactylnoradrenaline are here used to refer to compounds which are believed identical with those previously encountered in extracts of adrenal glands by Crawford. METHODSCollection of Adrenal Glands.-Adrenal glands were removed from spinal cats or from cats under anaesthesia (e...

The Transmitter Released by Stimulation of the Bronchial Sympathetic Nerves of Cats

“…3 and 4). Throughout the present work either the uterus or the colon was taken from a strain of rats which were normally sensitive to isoprenaline, but which were abnormally insensitive to adrenaline (Lockett, 1954). Table IV shows that the amine released by stimulation of adrenergic nerves to the lungs could not be distinguished from isoprenaline, but was clearly differentiated from adrenaline by these methods.…”

“…The chemical transmitter of the postganglionic sympathetic nerve fibres supplying bronchi was examined because isoprenaline (Konzett, 1940a) and the third amine of the adrenal gland (Lockett, 1954) had proved more active than adrenaline as dilators of previously constricted bronchioles. Cats were selected for this investigation because the third amine of the adrenals was known to occur in this species (Lockett, 1954). …”

Pharmacological Observations on the Hypotensive Action of Extracts of Teleost Fish Urophyses (Urotensin I) in the Rat

“…Further, urotensin does not act by causing a prolonged release of acetylcholine, histamine or an isoprenaline-like metabolite of adrenaline. Such a metabolite of adrenaline has been shown to be present in extracts of mammalian adrenal medulla (Lockett, 1954), in extracts of protein-free plasma of rabbits (Roberts & Lockett, 1961), or released in a cat heart-lung preparation after stimulation of sympathetic chains (Lockett, 1957).…”

The Chemical Estimation of Epinephrine and Norepinephrine in Human and Canine Plasma. I. A Critique of the Ethylenediamine Condensation Method 1

“…Among the catechol substances which have been reported present in human urine, tissue extracts, or blood are: 1 ) isopropylnoradrenaline, tentatively identified by Lockett (15) in the adrenal medulla; 2) dopamine, found in urine (1), and 3) dopac which has been tentatively identified in urine by von Euler, von Euler, and Floding (2). Dopa has not been shown to be present in tissue or biological fluids, nor has dihydroxyphenylserine, and isopropylnoradrenaline constitutes less than one per cent of the E and N in the human adrenal medulla (15). Therefore, the principal possibilities for the substances detected in plasma eluates by the EDA method (but not by the trihydroxyindole method) appear to be dopamine and its supposed metabolite dopac.…”