‘A beautiful but remote lady’
To most of the modern pharmacologists the receptor is like a beautiful but remote lady. He has written her many a letter and quite often she has answered the letters. From these answers the pharmacologist has built himself an image of this fair lady. He cannot, however, truly claim ever to have seen her, although one day he may do so[1].
So wrote Dutch pharmacologist D.K. de Jongh as recently as 1964. For him and others, the cell receptor was something of an enigma. Not least, there was the problem of understanding how cells seemed to boast receptors for manmade chemical substances synthesized in the laboratory. For German professor of pharmacology Klaus Söhring speaking at a colloquium in Hamburg in the early 1950s, this conundrum was so great that it all but ruled out the existence of such specific receptors. After all, he argued, how could God, the Creator, have known which different kinds of pharmaceutical substances would be developed by mankind [2].
Such doubts about receptors were only dispelled with the development of the first receptor-specific remedies, in particular the beta-receptor blockers for the therapy of hypertension and the histamine-H2-receptor blockers for the treatment of stomach ulcers. James Black, who was the originator of both these groups of drugs, was awarded the Nobel Prize for Medicine or Physiology in 1988 [3]. By this time other researchers had elucidated the protein structure and genetic basis of various other receptors and had even visualised some of them with electron microscopy. It became increasingly clear that the human body contained many hundreds of receptor subtypes, opening up a vast new field of research to the pharmaceutical industry. The aim was to target these receptors for the specific treatment of various diseases, ranging from cystic fibrosis to epilepsy [4].
Given the ubiquity of receptors in today's biomedical sciences, it is worth looking into the history of these molecules in more detail. In particular, where did the concept of a receptor come from, why was concrete evidence for its existence so long in coming and what role did the notions of substance binding and of specific effects of substances play in this process?