Introductory RemarksAuthor(s): Arnold BurgenSource: Proceedings of the Royal Society of London. Series B, Biological Sciences, Vol. 210, No.1178, Neuroactive Peptides (Oct. 29, 1980), pp. 3-4Published by: The Royal SocietyStable URL: http://www.jstor.org/stable/35412 .

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Proc. R. Soc. Lond. B 210, 3-4 (1980)

Printed in Great Britain

Introductory remarks

BY SIR ARNOLD BURGEN, F.R.S.

National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 IAA, U.K.

It was in 1895 that Oliver & Schafer discovered the pressor activity of glycerol extracts of the pituitary. By 1928 it was clear that this activity, called vasopressin, was due to a peptide derived from the neural lobes of the pituitary and, in the early fifties, its structure and that of its 'twin', oxytocin, were determined by du Vigneaud and his colleagues, who were also able to prepare them synthetically. For a long time these two peptides, which were clearly of neural origin, were thought to have only peripheral physiological actions. However, evidence has gradually accumulated that these as well as some hormonal peptides not of neural origin, such as angiotensin and corticotrophin, could have actions on the central nervous system.

The discovery of the enkephalins by Hughes & Kosterlitz in 1975 revealed the presence of an oligopeptide in the forebrain that could influence brain function and for which a specific receptor could be delineated which provided an immediate connection with the well documented non-peptide analgesic drugs of the morphine group. Within a short time discrete localization both of enkaphalin stores and of enkephalin receptors within the nervous system was demonstrated. In the ensuing period a growing number of peptides have either been isolated from the brain or have been inferred, from immunological evidence, to be present. Some of these peptides, such as insulin and gastrin, have well established peripheral biological actions, and their presence in the brain has engendered considerable surprise.

It is clear that the subject of neuroactive peptides is one in which even the basic facts of the identity and diversity of peptides is still far from clear. The generation of peptides from larger precursor units and the ready further processing and degradation by peptidases make these questions peculiarly difficult to answer. Nevertheless, one cannot proceed sensibly without posing some taxing functional questions. Because we find a peptide in the brain, does it necessarily have a role in brain function? If it does, what is this role? Is it a synaptic transmitter, or a short-term modulator of a non-peptide transmitter? What is the meaning of the finding in several systems of concomitant release of a peptide and a small molecule transmitter? Are peptides concerned with neural development or remodelling or with some aspect of cellular metabolism? Are at least some of them functionl3ss signposts of ontogeny or phylogeny? These are all questions to bear in mind as we hear presentations in this meeting. There is also a chemical puzzle that is begging for imaginative solutions. It is very difficult to compare the structure of oligo- peptides with the structure of non-peptide molecules, such as heterocycles or

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4 Introductory remarks

steroids, yet the biological facts that enkephalin shares properties with morphine and can share a receptor forces us to seek structural relationships.

There is no doubt about the timeliness of this meeting, which has been made abundantly clear by the overwhelming number of applications to attend it.

Thanks are due to the Wellcome Trust for its contribution towards the cost of organizing the meeting.

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