The action of adrenalin

Elliott, T. R.

doi:10.1113/jphysiol.1905.sp001093

Cited by 426 publications

(103 citation statements)

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“…In May 1904, in a preliminary communication to the Physiological Society, the young researcher made hisÐ today famousÐsuggestion, that adrenalin was``secreted by the sympathetic paraganglia'' and might be``the chemical stimulant liberated on each occasion when the [nervous] impulse arrives at the periphery''. 60 While this proposal has placed Elliott firmly in the history of the concept of chemical neurotransmission, 61 his thoughts on how the muscle cell received the stimulus of the``chemical excitant'', and reacted with a change of tension of the muscle fibres, were important for the development of the receptor idea.…”

Section: The Idea Of Receptive Substancesmentioning

confidence: 99%

“Receptive Substances”: John Newport Langley (1852–1925) and his Path to a Receptor Theory of Drug Action

Maehle

2004

Med. Hist.

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The concept of specific receptors that bind drugs or transmitter substances onto the cell, thereby either initiating biological effects or inhibiting cellular functions, is today a cornerstone of pharmacological research and pharmaceutical development. Yet, while the basic ideas of this concept were first explicitly formulated in 1905 by the Cambridge physiologist John Newport Langley (1852–1925), drug receptors remained hypothetical entities at least until the end of the 1960s. Without doubt, the development of receptor-subtype specific pharmaceuticals—especially the beta-adrenergic receptor antagonist propranolol (introduced in 1965)—promoted the acceptance of the receptor concept in pharmacology. It was only in the 1970s, however, that receptors began to be isolated as specific proteins of the cell membrane and that their composition and conformation began to be explored. During the last twenty years the modern techniques of molecular biology have helped to determine the genetic basis of receptor proteins, to identify their amino acid sequences, and to further elucidate their remarkable structural diversity as well as their similarities and evolutionary relationships. Numerous receptor types and subtypes have since been characterized.

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Section: The Idea Of Receptive Substancesmentioning

confidence: 99%

“Receptive Substances”: John Newport Langley (1852–1925) and his Path to a Receptor Theory of Drug Action

Maehle

2004

Med. Hist.

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“…Chief among these are a reduction in circulating blood volume with haemoconcentration (Bainbridge & Trevan, 1917;Erlanger & Gasser, 1919;Freeman et al, 1941); liberation of vasodilator substances, including histamine, or the vasodilator action of the infused sympathomimetic itself (Blacket et al, 1950;Gyorgy & D6da, 1960;Coppola & Dipalma, 1962); acidosis (Small, Weitzner & Nahas, 1959); and cardiac failure (Elliott, 1905;Chen & Schmidt, 1925;Chen, 1928;MUgge, 1932;Chappel, Rona, Balazs & Gaudry, 1959;Szakacs & Mehlman, 1960). It is also true that each of these mechanisms at some other time has been excluded as the cause of the loss in response.…”

Section: Effect Of Prolonged Continuous Stimulation Of Sympathetic Nementioning

confidence: 99%

The Origin of the Decline in the Vasopressor Response to Infused Noradrenaline in the Pithed Rat

Gillespie¹,

Muir²

1967

British Journal of Pharmacology and Chemotherapy

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In several species, including man, the continuous infusion of noradrenaline always results in an eventual steady decline from the initial pressor level (Nickerson, 1962;Rosenthale & Dipalma, 1963;Beyth & Gutman, 1965). This reduction in response is usually attributed to desensitization or tachyphylaxis. Our interest in this phenomenon arose during attempts to modify that preparation of the anaesthetized rat described by Straughan (1958) as an assay method for acetylcholine. To overcome the large reflex depressor artefact which accompanies any intravenous injection in this preparation, the rat was pithed and the normal neurally maintained vascular tone mimicked by infusing noradrenaline continuously in amounts sufficient to raise the blood pressure to about 120 mm Hg. A highly sensitive and artefact-free preparation in which the effect of 0.25 ng of acetylcholine could be recognized was obtained. However, within 5 10 min of beginning the infusion both the blood pressure and the sensitivity to acetylcholine began to fall. Two points seemed of interest. First, if this were due to desensitization to noradrenaline, it was not specific for one substance. Secondly, although the noradrenaline infused was limited to that required to match the neurally released transmitter in restoring the blood pressure to normal levels, desensitization still occurred. Previous investigations of this phenomenon have employed animals with an intact vasoconstrictor outflow in which the infused noradrenaline raised the blood pressure above normal.The present paper reports the results of an investigation into the causes of these changes. The literature contains few reports which allow the contribution of the peripheral vascular smooth muscle to the fall in blood pressure to be separated from that of the heart. To do this, a modification of the technique of Bygdeman (1963) was used, in which the isolated vascular bed of one lower limb was perfused in situ with the animal's own arterial blood. The perfusion pressure gave a measure of the response of the vascular smooth muscle uncomplicated by cardiac efficiency. The blood pressure response of the whole animal, excluding the perfused limb, gave an integrated picture of both the peripheral vascular response and the ability of the heart to maintain its output in face of any increase in peripheral resistance. * Henry Head Fellow.

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“…They thought that the actions of chemicals were too slow to mediate the rapid effects of neurotransmission. But Thomas Elliott, a student of John Langley's, suggested in 1905 that epinephrine might be released by sympathetic nerves (Elliott, 1905). This hypothesis arose from his studies of the effects of adrenalin/epinephrine on the sympathetic nervous system.…”

Section: Significance Statementmentioning

confidence: 99%

Floyd Bloom Discusses the Messengers of the Mind

Esch

2015

eNeuro

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The action of adrenalin

Cited by 426 publications

References 0 publications

“Receptive Substances”: John Newport Langley (1852–1925) and his Path to a Receptor Theory of Drug Action

“Receptive Substances”: John Newport Langley (1852–1925) and his Path to a Receptor Theory of Drug Action

The Origin of the Decline in the Vasopressor Response to Infused Noradrenaline in the Pithed Rat

Floyd Bloom Discusses the Messengers of the Mind

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