Reflections on Substance P and Some Related Peptides
In contrast to many other peptides, substance P was right away purified both from intestine and brain. This may be regarded as a sign of the remarkable intuition that characterized Ulf von Euler’s research throughout his career. In this way substance P never belonged to the many gastrointestinal peptides which to our surprise later on also were discovered in the brain. The research which followed the original discovery of substance P by von Euler and Gaddum (15) has exhibited a wavy pattern with bursts of activity appearing at shorter and shorter intervals, as schematically indicated in Figure 1. Thus, substance P research was slow after the initial studies until the 50’ s, when several groups initiated new efforts, including researchers such as Lembeck, Pernow, Umrath and Zetler, resulting i.a. in an extensive mapping of distribution of substance P activity in various tissues (12) as well as the suggestion that substance P could act as transmitter substance in primary sensory neurons (9). Although interest in substance P remained in the following years, no dramatic events occurred until the beginning of the 70’ s, when Susan Leeman and her collaborators sequenced substance P and showed that it represents a peptide consisting of eleven amino acids. Subsequently this group synthesized substance P, raised antisera and worked out a radioimmunoassay (RIA). This major progress led to intense activity in many laboratories allover the world. The work in Masanori Otsuka’s laboratory was seminal in defining a functional role for substance P and, for example, at the Karolinska Institute Bengt Pernow initiated a new wave of substance P research. In the following years the distribution of substance P was outlined both with radioimmunoassay and immunohistochemistry, and novel aspects of the function of substance P were outlined. We remember particularly Jim Henry’s work on a possible involvement of substance P in pain transmission, and the elucidation by Fred Lembeck and his associates of the role of substance P in the axon reflex.
KeywordsDopamine Amidated Polypeptide Phenylalanine Nism
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