Avian opioid peptides: evolutionary considerations, functional roles and a challenge to address critical questions.

The present review considers the putative hormonal opioid peptides in birds. In birds and all other vertebrates, there are four opioid related genes encoding a series of peptides. These genes are, respectively, proenkephalin (PENK), prodynorphin (PDYN), pronociceptin (PNOC) and proopiomelanocortin (POMC). Proenkephalin (PENK) encodes Met- and Leu-enkephalin together with peptides containing met enkephalin motifs in birds, mammals and reptiles. Proopiomelanocortin (POMC) encodes β endorphin together with adrenocorticotropic hormone (ACTH), and melanocyte stimulating hormone (MSH). Prodynorphin (PDYN) encoding dynorphins A and B with α- and β-neoendorphins together intermediate polypeptides across the vertebrates. Pronociceptin (PNOC) encodes nociceptin together with possibly putative avian nocistatin and a non-opioid peptide derived from the C terminal of pronociceptin. There is a high degree of identity in the sequences of enkephalin peptides, dynorphin-A and B and nociceptin in birds and, to a less extent, across vertebrates. The opioid peptides exert effects related to pain together with other biological actions such as growth/development acting via a series of opioid receptors. What is unclear, particularly in birds, is the biological roles and interactions (additivity, antagonistic and synergistic) for the individual opioid peptides, the processing of the prohormones in different tissues and the physiological relevance of the different peptides and, particularly, of the circulating forms.