RESUMEN
The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.
Asunto(s)
Acetilcolina/historia , Amanita/química , Muscarina/historia , Acetilcolina/fisiología , Asma/tratamiento farmacológico , Asma/historia , Antagonistas Colinérgicos/historia , Antagonistas Colinérgicos/uso terapéutico , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Muscarina/aislamiento & purificación , Pilocarpina/historia , Pilocarpina/aislamiento & purificación , Pilocarpina/uso terapéutico , Pilocarpus/química , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/historia , Receptores Colinérgicos/historia , Receptores Colinérgicos/fisiología , Chamanismo/historiaRESUMEN
The 50th anniversary of the classic Monod-Wyman-Changeux (MWC) model provides an opportunity to survey the broader conceptual and quantitative implications of this quintessential biophysical model. With the use of statistical mechanics, the mathematical implementation of the MWC concept links problems that seem otherwise to have no ostensible biological connection including ligand-receptor binding, ligand-gated ion channels, chemotaxis, chromatin structure and gene regulation. Hence, a thorough mathematical analysis of the MWC model can illuminate the performance limits of a number of unrelated biological systems in one stroke. The goal of our review is twofold. First, we describe in detail the general physical principles that are used to derive the activity of MWC molecules as a function of their regulatory ligands. Second, we illustrate the power of ideas from information theory and dynamical systems for quantifying how well the output of MWC molecules tracks their sensory input, giving a sense of the "design" constraints faced by these receptors.
Asunto(s)
Modelos Biológicos , Modelos Moleculares , Receptores Colinérgicos/historia , Animales , Fenómenos Biomecánicos , Historia del Siglo XX , Historia del Siglo XXI , HumanosAsunto(s)
Acetilcolina/historia , Acetilcolina/metabolismo , Electrofisiología/historia , Neurotransmisores/historia , Receptores Colinérgicos/historia , Transmisión Sináptica , Potenciales de Acción , Animales , Historia del Siglo XX , Humanos , Desnervación Muscular , Músculo Esquelético/inervación , Unión Neuromuscular/metabolismo , Neurotransmisores/metabolismo , Receptores Colinérgicos/metabolismo , Factores de TiempoRESUMEN
This article traces the development of knowledge about the physiology and pharmacology of acetylcholine and its receptors between 1930 and 2005, with emphasis on contributions by members of the British Pharmacological Society, and by other British pharmacologists and physiologists.