Exorphins: peptides with opioid activity isolated from wheat gluten, and their possible role in the etiology of schizophrenia

Abstract

Endogenous opioid peptides, the endorphins (including enkephalin) are extremely potent substances which exert their effect at concentrations in the nanomolar range (Hughes et al., 1975; Lord et al., 1977; Klee, 1977). Furthermore, even though endorphin receptors are very specific, many structural variations are tolerated, albeit often with some loss of potency (Terenius et al., 1976a; Ling and Guillemin, 1976; Chang et al., 1976; Coy et al., 1976; Schiller et al.; 1977, Agarwal et al., 1977; Beddell et al., 1977). Nevertheless, peptides with as little as 1 per cent of the activity of enkephalin will still be potent and could have profound pharmacological effects. Food proteins which happen to contain the appropriate peptide sequences, related to but not necessarily identical with those of the enkephalins could therefore be a natural source of opioid peptides. Such peptides might logically be called ‘exorphins’, since they are exogenously derived substances with morphine-like activity. We have found exorphin activity in pepsin digests of wheat gluten, a protein known to be arimar factor in the pathology of celiac disease, and postulated by Dohan (1966a) to be also involved in the etiology of schizophrenia.