A binding question: the evolution of the receptor concept

Abstract

In present-day pharmacology and medicine, it is usually taken for granted that cells contain a host of highly specific receptors. These are defined as proteins on or within the cell that bind with specificity to particular drugs, chemical messenger substances or hormones and mediate their effects on the body. However, it is only relatively recently that the notion of drug-specific receptors has become widely accepted, with considerable doubts being expressed about their existence as late as the 1960s. When did the receptor concept emerge, how did it evolve and why did it take so long to become established?

The Hill equation and the origin of quantitative pharmacology

“…Paul Ehrlich (1854-1915) developed a similar hypothesis starting from the results of his bacteriological investigations in 1897 (Maehle 2009). They refined these ideas in close competition, which is also reflected in the terms they used to describe the specific chemical structure on the cell receiving the agent evoking a cellular response: "side chain" (Ehrlich in 1897), "receptor" (Ehrlich in 1900; the term proved to be enduring), and "receptive substance" (Langley in 1905) (Maehle 2004(Maehle , 2009). The receptor concept can be summarized by the classic maxim of Ehrlich: "Corpora non agunt nisi fixata" (agents do not act unless they are bound) (Pelner 1972).…”

“…The suggestion that both exogenous and endogenous agents must be specifically bound to structures inherent to the living organisms before exerting an effect was first proposed by John Newport Langley in 1878, based on his experiments on salivary secretion in the dog (Maehle 2004). Paul Ehrlich (1854-1915) developed a similar hypothesis starting from the results of his bacteriological investigations in 1897 (Maehle 2009). They refined these ideas in close competition, which is also reflected in the terms they used to describe the specific chemical structure on the cell receiving the agent evoking a cellular response: "side chain" (Ehrlich in 1897), "receptor" (Ehrlich in 1900; the term proved to be enduring), and "receptive substance" (Langley in 1905) (Maehle 2004(Maehle , 2009).…”

“…The receptor theory is widely thought to be the concept most characteristic for pharmacology (Kenakin 2004;Colquhoun 2006;Rang 2006;Maehle 2009). Following preliminary suggestions by Langley and Ehrlich, Joseph Clark established the first comprehensive receptor theory, the so-called occupation (or occupancy, or traditional receptor-stimulus) theory (Clark 1926).…”

Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects

“…Clark [40] also had some experience in the study of dose-responses, observing a biological threshold for acetylcholine that required approximately 20,000 molecules acting via receptors to produce an initial effect on a heart cell (e.g., isotonic contraction). Clark had been a professor working in Cushny's department and twice replaced him as Department Chair (at the University of London, 1920, and then at Edinburgh, after Cushny's death in 1926) [41,42]. Such research on the threshold concept was further extended in the laboratory of the Nobel Prize winner and British pharmacologist Charles Scott Sherrington, by Russell Aitken and his advisor J.G.…”

Receptor A2a de adenosina: estudo da modulação da liberação de neurotransmissores em modelo in vitro

“…Contemporaneamente, Paul Ehrlish desenvolveu sua própria teoria sobre receptor, que ele chamou de "quimioreceptor", assim como, também descobriu o arsênico Salvarsan, o primeiro agente quimioterâpitico usado no tratamento da sífilis(Maehle., 2009).…”