Pharmacologically active substances formed in egg yolk by cobra venom

Vogt, W.

doi:10.1113/jphysiol.1957.sp005748

Cited by 63 publications

(16 citation statements)

References 17 publications

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“…The method of staining unsaturated compounds on paper by exposure to 0804 vapour (Hack, 1953;Vogt, 1957b) was insufficiently sensitive to reveal the minute quantities of irin in the active areas of electrophoresis papers. The evidence that irin is unsaturated is based on its inactivation by oxidation with KMnO4, by catalytic hydrogenation and by halogenation with IBr (or by chlorine gas).…”

Section: Rc-omentioning

confidence: 99%

Further studies on the preparation, purification and nature of irin

Ambache¹

1959

The Journal of Physiology

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Distilled water extracts of rabbit iris contain an acid which is physiologically active on certain smooth muscles (Ambache, 1957a). Improvements in the purification and assay of this substance are now described and also an investigation of its chemical nature. First, a number of acids of biological origin have been screened for activity. Although representative of a variety of structuretypes, the acids examined are nearly all inactive or can be otherwise distinguished from irin. Direct evidence is then produced that irin is a long-chain unsaturated hydroxy-fatty acid. Further structure-action studies on available hydroxy-acids and lactones have shown that (+ )-ricinoleic acid is a powerful stimulant of the smooth muscle in the hamster colon, whereas oleic acid which lacks the hydroxyl group of ricinoleic but is otherwise identical with it, is relatively inert. These and other findings suggest that an OH group, a double bond, and the spatial relation between them, determine the irin-like activity of fatty acids. METHODSIrin. The source of active material has been the rabbit's iris throughout; although ox irides are larger and would have been more plentiful they contain less than &-O jO the activity found in rabbits' irides. The procedure for making iris extracts described in the previous paper was modified slightly as follows: (i) unless otherwise stated all extracts were made in distilled water (1 ml./ 100mg tissue) neutralized when necessary with 0.02% NaHCO3; (ii) as the pharmacological activity of'extracts is reduced by boiling, the heating was omitted-instead, the centrifuged extracts were left for some days at -15°C, which precipitates out further impurities removable by a second or third centrifugation; (iii) the irides were excised more rapidly, by direct removal through a slit in the cornea without prior enucleation of the eyes. I am indebted to Dr B. C. Whaler for'four extracts of several hundred irides prepared in this way at Porton. For these, the dried irides were ground, unweighed, in 0*4 ml. of distilled water per iris, i.e. assuming an average weight of 40 mg per iris; the dosage of these extracts is expressed in arbitrary units of' _ mg'; (iv) some extracts were prepared from irides excised a few hours after death. Through the courtesy of Dr M. Sterne the severed heads from rabbits killed at the Wellcome Research Laboratories in the morning were sent here, where the eyes were excised and the irides were extracted in the early afternoon. Such extracts were rather less active than those made from fresh irides.

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Section: Rc-omentioning

confidence: 99%

Further studies on the preparation, purification and nature of irin

Ambache¹

1959

The Journal of Physiology

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“…The special nature of the fatty portion, which is the cause of the lipid-solubility and the nature of the acidic groups, may be of minor importance. This suggestion is supported by the fact that other lipid-soluble acids, namely certain unsaturated fatty acids, also have smooth-muscle stimulating properties (Gabr, 1956;Vogt, 1956). …”

Section: Discussionmentioning

confidence: 93%

The chemical nature of Darmstoff

Vogt¹

1957

The Journal of Physiology

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The term Darmstoff was given to a smooth-muscle-stimulating substance which was first observed with bath fluid of isolated intestine preparations (Vogt, 1949). The substance is easily soluble in many organic solvents and is acidic in nature. These properties distinguish Darmstoff from amines and polypeptides (Vogt, 1955 (Vogt, 1955) in that it simplifies the extraction because the tissue is dissolved by the alkali. After cooling the solution it was made slightly acidic by adding HCI. A precipitate formed which, besides proteins, contained Darmstoff. The precipitate was collected by centrifugation and then extracted with 5 1. n-butanol. A clear butanol filtrate was obtained which was concentrated in vacuo after the addition of sufficient ammonia solution to prevent the filtrate from becoming acidic. The concentrate was purified by two counter current distributions in water-methanol-butanol-benzene and methylethylketonewater, as described earlier (Vogt, 1955). An amount of 418 mg dry weight of Darmstoff extract was obtained with an activity of 35,900 u./mg. The unit has been defined elsewhere (Vogt, 1953). The material was dissolved in butanol and stored for nearly a year before the present experiments were undertaken; some loss of activity may have occurred during this time. For use, suitable portions of this solution were taken and dried in a stream of N2. All weights given refer to the dry material.Preparation of Ba salt of Darmatoff. A sample of 18 mg of Darmstoff was dissolved in 5 ml. of a methanol-butanol mixture (1 + 1 vol.). On the addition of 0 3 ml. of a saturated BaCl2 solution in methanol a small precipitate formed. It had no smooth-muscle-stimulating effect on the rabbit duodenum and was therefore discarded. When the filtrate was made alkaline by the addition of 041 ml. N-NaOH, a new precipitate formed, which was collected by centrifugation after * British Council Scholar.

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“…This possibility must also be taken into account, since SRS-C and arachidonic acid are known to generate RCS from guinea-pig lungs perfused with Krebs solution (Vargaftig & Dao, 1971 a). SRS-C is a mixture of unsaturated fatty acids released from phospholipids by phospholipase A2 contained in snake venom (Vogt, 1957). It is possible that the hypotensive effect, as well as the generation of RCS from blood by SRS-C, is due to its content of unsaturated fatty acids, especially arachidonic acid.…”

Section: Discussionmentioning

confidence: 99%

Inhibition by Non‐steroid Anti‐inflammatory Agents of Rabbit Aorta Contracting Activity Generated in Blood by Slow Reacting Substance C

Ferreira

Vargäftig

1974

British J Pharmacology

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A crude and a partially purified preparation of slow reacting substance C (SRS-C) as well as arachidonic acid decreased resistance to perfusion of the dog hind paw. This effect was suppressed by treatment with non-steroid anti-inflammatory drugs. 2 Injections of SRS-C or of arachidonic acid induced marked and reproducible contractions of strips of rabbit aorta and a rat stomach which were bathed in blood from an anaesthetized dog. The effect on the rabbit aorta is attributed to formation of a rabbit aorta contracting substance (RCS). The contractions were suppressed when the dog was treated with a non-steroid anti-inflammatory drug. 3 Incubation of blood or of platelet-rich plasma with SRS-C or arachidonic acid resulted in the formation of similar materials. This formation was suppressed by anti-inflammatory drugs. 4 SRS-C, linoleic, linolenic, and arachidonic acids are suitable substrates for soybean lipoxidase for the generation of RCS. 5 It is suggested that RCS and prostaglandin are formed within platelets, when SRS-C or arachidonic acid are injected into animals or added in vitro. Non-steroid anti-inflammatory drugs suppress these effects, possibly by inhibiting prostaglandin synthetase.

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Pharmacologically active substances formed in egg yolk by cobra venom

Cited by 63 publications

References 17 publications

Further studies on the preparation, purification and nature of irin

Further studies on the preparation, purification and nature of irin

The chemical nature of Darmstoff

Inhibition by Non‐steroid Anti‐inflammatory Agents of Rabbit Aorta Contracting Activity Generated in Blood by Slow Reacting Substance C

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