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OR genes coexpressed in the same OSN have related expression patterns in adults, suggesting regional biases that restrict OR gene activation to a subset of OR genes.

However, a single OSN can coexpress genes located on multiple chromosomes, arguing against the possibility that coexpression of multiple OR genes results from chromatin changes at a single locus containing those genes.

In other studies, we have developed viral tracers to explore how volatile predator odors induce fear-associated increases in stress hormones, which are controlled by hypothalamic corticotropin releasing hormone (CRH) neurons.

We found that the amygdalo- piriform transition area (Am Pir), a minor area of the olfactory cortex, plays a key role in this response and that the hormonal and behavioral components of the fear response are likely to involve different olfactory cortical areas.

Most recently, we have found that the intestinal brush border disaccharidase enzymes maltase and sucrase are expressed in T1R3 taste cells.

In both wildtype and T1R3 knockout mice disaccharidase inhibitors significantly reduced gustatory nerve responses to the disaccharides sucrose and maltose, but not to the monosaccharides glucose and fructose or the noncaloric sweeteners.

The long-term objective of these studies is to provide insights into the brain mechanisms that link emotion and decision-making, and their evolutionary origins.It appears that these orally expressed enzymes act in concert with salivary amylase to generate free glucose from sucrose, maltose and starch that can activate the T1R3-independent sugar detection pathway.In sum our studies point out similarities in gustation and gut chemosensation and indicate the importance of “taste cells of the gut” and “endocrine cells of the tongue” in coordinating the body’s hormone responses to regulate glucose homeostasis.We have found that intestinal endocrine cells express sweet taste receptors, gustducin, and several other taste transduction elements.Knockout mice lacking gustducin or the sweet taste receptor subunit T1R3 have deficiencies in secretion of GLP-1 and in the regulation of plasma levels of insulin and glucose.Moreover in 1999, we discovered ghrelin from the stomach as an endogenous ligand for the growth hormone (GH) secretagogues receptor (GHS-R), an orphan GPCR.Beside the potent stimulatory effect of GH release, ghrelin is also involved in the stimulation of feeding and the regulation of energy metabolism.Our most recent topic is “atrial natriuretic peptide prevents cancer metastasis through inhibition of cancer cell adhesion to vascular endothelial cells”. This question is a beginning of our most recent challenge. In this lecture, I will briefly summarize my challenge to novel peptide hormones over 40 years; their discoveries, physiological significance and therapeutic potentials.We are interested in the mechanisms underlying the sense of smell and instinctive odor responses in mammals.In the course of these studies, we discovered novel bioactive peptides such as three natriuretic peptides, ANP (1984), BNP (1988) and CNP (1990), in mammalian heart and brain, and adrenomedullin (1993) in human pheochromocytoma.The identification of ANP from the human heart elucidated a new regulatory mechanism of cardiovascular system by the peptide hormone from the heart.

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