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

Abstract

A study has been made of the transmitter released in a cat heart-lung preparation when the sympathetic chains were stimulated. The nervi accelerantes were always sectioned before stimulation. The transmitter appeared first in the pulmonary venous blood. In its actions on the heart-lung preparation, it resembled isoprenaline and not adrenaline. Chromatographic studies using three different solvents showed that 80 to 100% of this transmitter consisted of a catechol amine which had R, values which were identical with those of isoprenaline. Pharmacological studies failed to distinguish between the actions of this amine and those of isoprenaline, but clearly differentiated between those of the pulmonary amine, adrenaline, and noradrenaline.The discovery of trace amounts of a third sympathomimetic amine in saline extracts of the adrenal -lands of cats, monkeys, and man has been reported by Lockett (1954). This amine could not be differentiated from isoprenaline (N-isopropylnoradrenaline) by its colour reactions, by its chromatographic behaviour, or by its pharmacological activity; it could, however, readily be distinguished from adrenaline and from noradrenaline both in R, values and by pharmacological means.The possible physiological significance of this trace amine required study. 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). METHODSThe experiments recorded involved 123 cats.Anaesthesia was induced with chloroform and ether (1:4 parts v/v) and was maintained with chloralose, 8 ml./kg. of a 1% w/v solution in 0.9% w/v NaCl in water, given by femoral venous cannula. The anticoagulant used was heparin (Liquemin, Roche), 500 units/kg. body weight. Donor blood, containing very little adrenaline and noradrenaline, was obtained as follows: anaesthetized cats were made spinal, the adrenals were excluded from the circulation, and the sympathetic chains were removed from just above the stellate ganglia to the brim of the pelvis. After an interval of 20 min. the cats were bled from a carotid arterial cannula.Heart-lung preparations were made in adrenalectomized spinal cats by a technique essentiallyifiiiiar tdtimartused by Knowlton and Starling (1912). Systemic outflow was recorded from a simple syphon placed between the peripheral resistance and the reservoirs. The circuit was arranged to allow the return of blood from the syphon recorded to either of two reservoirs. These reservoirs were small double surface condensers, each of 60 ml. maximum capacity. Blood from either reservoir was returned to the heart through a 4 in. Liebig condenser which adjoined the cannula in the superior vena cava. The reservoirs and the Liebig condenser were warmed with water whi...

Pharmacological significance of biogenic amines in the lungs: noradrenaline and dopamine

“…The evidence that the bronchodilator fibres are adrenergic is mainly pharmacological. Lockett (1957) observed that the sympathetic bronchodilator fibres can be blocked by compound TM-1O (Choline 2: 6-xylyl ether bromide), which is thought to act by preventing the release of the transmitter substance. Daly & Mount (1951) noted that response to stimulation of the bronchodilator fibres can be potentiated by cocaine, an effect thought to be mediated by an action on the adrenergic fibres.…”

“…Daly & Mount (1951) noted that response to stimulation of the bronchodilator fibres can be potentiated by cocaine, an effect thought to be mediated by an action on the adrenergic fibres. Furthermore, Lockett (1957) has reported the release of an isoprenaline-like substance in the perfusate of the cat heart-lung preparation, following electrical stimulation of the thoracic sympathetic chain. Muscholl & Vogt (1958), however, used more stringent methods of identification and were unable to confirm the release of isoprenaline.…”

Circulatory, respiratory and metabolic responses to isopropylnoradrenaline in man

“…Since trace amounts of this amine have been reported in the adrenal glands of the cat, monkey and man (Lockett, 1954) and in the pulmonary venous blood of cats after stimulation of the cervical sympathetic chain (Lockett, 1957), a more detailed study has been made of its circulatory, respiratory and metabolic effects in man; a preliminary summary of the findings has already been reported (Cobbold, Galbraith, Ginsburg & Paton, 1958). …”

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).…”