Regulatory peptides represent the most diverse and versatile family of messenger molecules. They are produced by all living organisms from bacteria to mammals. They are involved in a wide variety of biological functions. Biologically active peptides and their receptors thus constitute an unlimited source of inspiration for the development of innovative drugs and cosmetics. The present eBook is a unique collection of research articles and reviews that provide a representative examplification of the latest progress in regulatory peptide research.

J. M. Polak and S. R. Bloom For some time Experientia has published, as a unique feature, interdis ciplinary multi-author reviews, giving a comprehensive overview of sub jects regarded as 'growing edges' of science. The enthusiasm shown by the readers was contagious and thus it was felt necessary to compile a special volume dealing with the novel aspects of regulatory peptides. This book covers some of the growing areas in regulatory peptide research and, although it is based on the original volume of Experientia, it is expanded and updated. The topic of 'regulatory peptides' is relatively young and has grown at an unprecedented pace, from the embryonic conception of 'gut hor mones' or 'brain neuropeptides' some 15 years ago to the realisation that these active pep tides are found, almost without exception, in every part of l8 23 the body in all vertebrate and many invertebrate species • Why the term 'regulatory peptides'? It represents a convenient label encompassing both the active peptides present in nerves, which are re leased as (putative) neurotransmitters, and those in endocrine cells, which act locally or at a distance as circulating hormones, these being the l8 main components of the so-called diffuse neuroendocrine or APUD 17 system • Morphological studies support this physiological viewpoint.

This Research Topic features recent developments in the field of regulatory peptide physiology and peptide-based therapeutics.

Strictly speaking, the term regulatory peptides may include any peptide which has a regulatory function in any organism. In recent years, how ever, the term has come to mean those originally classified as brain-gut peptides. The peptides initially defined as those belonging to the brain gut axis had a dual location in neurones of the brain and endocrine cells of the gut. We now include a number of neuropeptides found in the autonomic nervous system of the gut, the cardiovascular system and other systems. To many scientists comparative physiology means comparison of the mechanisms of certain functions in the rat, the guinea-pig, the cat and maybe some other mammal. If the philosophy is that man is the centre of the universe and other mammals can be used as 'models' of man, this may well be the most useful way to study the functions of the human being, without actually chopping somebody up. However, with a some what wider perspective on life, it is easy to see the importance of a full understanding of the function of all living organisms, in its own right as well as a link in the evolution towards individuals able to survive and reproduce in very different environments. The importance of com parative studies in all living organisms cannot be emphasized too much. It has been the ambition with this book to treat all animals as equally important.

In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro." Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

The most comprehensive and conceptual one-volume treatment of this field available and the first to emphasize the cellular and molecular aspects of gut peptide biology. Authored by an array of internationally distinguished scientists, it deals with issues of peptide localization and biosynthesis in gastrointestinal cells, mechanisms of peptide release and inactivation and the nature of peptide receptors. The breadth and readability make it an invaluable reference source for scientists in all disciplines interested in any aspect of brain-gut peptides.

Peptide therapy has become a key strategy in innovative drug development, however, one of the potential barriers for the development of novel peptide drugs in the clinic is their deficiencies in clearly defined chemistry, manufacturing and controls (CMC) strategy from clinical development to commercialization. CMC can often become a rate-limiting step due to lack of knowledge and lack of a formal policy or guidelines on CMC for peptide-based drugs. Regulators use a risk-based approach, reviewing applications on a case-by-case basis. Peptide Therapeutics: Strategy and Tactics for Chemistry, Manufacturing, and Controls covers efficient manufacturing of peptide drug substances, a review of the process for submitting applications to the regulatory authority for drug approval, a holistic approach for quality attributes and quality control from a regulatory perspective, emerging analytical tools for the characterisation of impurities, and the assessment of stability. This book is an essential reference work for students and researchers, in both academia and industry, with an interest in learning about CMC, and facilitating development and manufacture of peptide-based drugs.

Regulatory peptides represent the most diverse and versatile family of messenger molecules. They are produced by all living organisms from bacteria to mammals. They are involved in a wide variety of biological functions. Biologically active peptides and their receptors thus constitute an unlimited source of inspiration for the development of innovative drugs and cosmetics. The present eBook is a unique collection of research articles and reviews that provide a representative examplification of the latest progress in regulatory peptide research.