Gluten Exorphins
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Gluten Exorphins

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Cat. # Product Name Price
G07003 Gluten Exorphin C Inquiry
G07001 Gluten Exorphin B5 Inquiry
G07002 Gluten Exorphin A5 Inquiry

Introduction

Gluten exorphins are a kind of opioid peptides, isolated from the pancreatic-elastase digest of wheat gluten. Gluten exorphins A and B have been found in the digests which were prepared by the further hydrolysis of the pepsin digest of wheat gluten with microbial neutral proteases such as thermolysin. There are four structure-known gluten exorphins: Gluten exorphin A5, Gluten exorphin B4, Gluten exorphin B5 and Gluten exorphin C. Gluten exorphins are related to the opioid excess theory or a part of leaky gut syndrome, which is a hypothesized process that people with schizophrenia and autism have the abnormal leakage from the gut of these compounds which then pass into the brain and disrupt brain function.

Mechanism of action

Gluten exorphins, which are exogenous opioids, bind to the same cellular receptors that endogenous opioids bind to. There is a study demonstrating that gluten exorphins A and B are released by the action of pepsin and pancreatic elastase. The sequence of gluten exorphin A5 is found 15 times in the primary structure of high molecular weight glutenin. In order for exorphins to function as opioid peptides in the central nervous system in vivo, they must meet the following conditions:

  • Be produced in the gastrointestinal tract
  • Survive degradation by intestinal proteases
  • Be absorbed, without degradation, into the bloodstream
  • Cross the blood-brain barrier and thereby reach central opiate receptors
  • Interact as opiates with these receptors.

Application of Gluten Exorphins

The gluten exorphin A5 stimulated the postprandial insulin release after the oral administration in rats and the effect was reversed by co-administration of naloxone. Therefore, it is possible that gluten exorphins A5 might be closely related to such a physiological function of the wheat gluten digests reported previously. Gluten exorphin B5 (Tyr-Gly-Gly-Trp-Leu) has the most potent in vitro activity and is agonistic on both μ and δ opioid receptors, among this family of peptides. In addition, the experimental results show that gluten exorphin B5 was used at the dose of 3 (mg/kg) body weight, which is the lowest dose able to elicit prolactin (PRL) response after peripheral administration. Gluten exorphin B5 stimulates PRL secretion after peripheral administration acting through opioid receptors located outside the blood-brain barrier (BBB), probably within the median eminence (ME), which indicated gluten exorphin B5 can modify brain neurotransmitter release without crossing the BBB. Furthermore, there was clinical evidence suggesting that removal of wheat gluten products from the diet leads to behavioural improvements for some autistic patients, which has been considered indirect evidence that gluten exorphins can be implicated in autism. However, the role of gluten exorphins in physiological and/or physiopathological conditions is still being investigated.

References
1. Fukudome, S. I., Jinsmaa, Y., Matsukawa, T., Sasaki, R., & Yoshikawa, M. (1997). Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS letters, 412(3), 475-479.
2. Cade, R., Privette, M., Fregly, M., Rowland, N., Sun, Z., Zele, V., & Edelstein, C. (2000). Autism and schizophrenia: intestinal disorders. Nutritional Neuroscience, 3(1), 57-72.
3. Yoshikawa, M., Takahashi, M., & Yang, S. (2003). Delta opioid peptides derived from plant proteins. Current pharmaceutical design, 9(16), 1325-1330.
4. Fanciulli, G., Dettori, A., Demontis, M. P., Tomasi, P. A., Anania, V., & Delitala, G. (2005). Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life sciences, 76(15), 1713-1719.

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