Arimura and co-workers, working in New Orleans, characterized pituitary adenylate cyclase-activating polypeptide (PACAP) some 13 years ago. Immediately after the discovery of this novel neuropeptide, my laboratory has embarked in the fierce competition engaged to elucidate the physiological relevance and pharmacological applications of PACAP. As a total, we have now published over 50 peer-reviewed papers on PACAP during the last decade. In particular, we have demonstrated that PACAP acts as a neurotrophic factor in cerebellar granule cells during postnatal development and we have shown that PACAP can prevent the deleterious effects of ethanol and oxidative stress in neurons. Since the discovery of PACAP, more than 1,000 papers have described the various biological aspects of this fascinating neuropeptide, so that it is extremely difficult to follow up the abundant literature in this exploding field. While several excellent reviews have focused on particular facets of PACAP, our paper, totaling 56 journal pages, provides the first comprehensive survey on the biochemical, physiological, and pharmacological knowledge on this peptide.

Owing to the plethoric literature already published on PACAP, I believe that many researchers found our review convenient for rapidly extracting the relevant information they need. Since we performed an exhaustive survey of the literature on PACAP and its receptors, other researchers involved in this field have probably been encouraged to refer back to our paper regularly.

Yes. The aim of our paper was to provide a survey comprehensively covering the previous literature on the structure and functions of PACAP and its receptors.

PACAP was originally discovered because of its ability to stimulate the activity of pituitary cells. Since then, a number of studies (several of which were conducted in my laboratory) have shown that PACAP and its receptors are widely expressed in the central nervous system and in peripheral organs. In addition, the structure of PACAP has been strongly conserved during evolution from tunicates (protochordates) to humans, suggesting that this novel neuropeptide likely serves important biological functions. Indeed, there is now clear evidence that PACAP acts as a neurohormone, a neurotransmitter, a neuromodulator and a neurotrophic factor. Moreover, it has been recently shown that PACAP can prevent neuronal death induced by alcohol consumption, stroke, and oxidative stress, suggesting that PACAP-derived drugs could have a therapeutical value for the treatment of various neurodegenerative diseases.

In collaboration with Professor Akira Arimura, I am currently editing a textbook on PACAP that will be published soon in the series Endocrine Updates, by Kluwer Academic Publishers.

Hubert Vaudry,
Director of Research at INSERM
Director of the European Institute for Peptide Research (IFRMP 23)
Director of the INSERM Unit 413
University of Rouen, France