History of key regulatory peptide systems and perspectives for future research

Abstract

Throughout the 20th Century, regulatory peptide discovery advanced from the identification of gut hormones to the extraction and characterization of hypothalamic hypophysiotropic factors, and to the isolation and cloning of multiple brain neuropeptides. These discoveries were followed by the discovery of G‐protein‐coupled and other membrane receptors for these peptides. Subsequently, the systems physiology associated with some of these multiple regulatory peptides and receptors has been comprehensively elucidated and has led to improved therapeutics and diagnostics and their approval by the US Food and Drug Administration. In light of this wealth of information and further potential, it is truly a time of renaissance for regulatory peptides. In this perspective, we review what we have learned from the pioneers in exemplified fields of gut peptides, such as cholecystokinin, enterochromaffin‐like‐cell peptides, and glucagon, from the trailblazing studies on the key stress hormone, corticotropin‐releasing factor, as well as from more recently characterized relaxin‐family peptides and receptors. The historical viewpoints are based on our understanding of these topics in light of the earliest phases of research and on subsequent studies and the evolution of knowledge, aiming to sharpen our vision of the current state‐of‐the‐art and those studies that should be prioritized in the future.

Neuroendocrine mechanism of gastric acid secretion: Historical perspectives and recent developments in physiology and pharmacology

“…In 1966, Håkanson observed dopamine-containing epithelial cells in the oxyntic mucosa of rats that had been injected with L-DOPA and this cell population was morphologically indistinguishable from 5-hydroxytryptaminecontaining EC cells. 16 A year later, Håkanson found that the ECL cells contained histamine [17][18][19][20] (Figure 1).…”

Advances in peptide modulation in systems physiology

“…Chen et al 8 describe not only how gastrin, but other gut peptides and transmitters exert overall control of gastric acid secretion, providing a specific description of a complex physiological event controlled by multiple first messengers, and the critical role played by regulatory peptides in its coordination, as well as involvement in its pathological manifestations, including cancer. Chen et al 9 place RegPep24 in the framework of the overall context of regulatory peptide research, and its rich and fascinating history. This perspective highlights the prospects for future therapeutics, and the problems to be solved in achieving clinical regulatory peptide ‘wins’, for the benefit of those within the field, and drug discovery watchers in general.…”