U.S. Department of Health and Human Services

New Function Identified for Odor Receptors

​A family of complex cell-surface receptors, some of which were initially characterized as playing a role in detecting odors in the nose, has since been found to be involved in the kidney’s integration of signals from gut microbial metabolism and the regulation of blood pressure.

These specific cell-surface receptors are members of a family of proteins known as seven-transmembrane receptors, so-called because the proteins snake back and forth across the outer cell membrane seven times, forming a complex structure that helps the cell sense and respond to molecules that are outside of the cell. At least six members of the larger receptor family have been identified in the kidney, where they appear to inluence the release of the hormone renin, which helps to regulate blood pressure by inluencing the amount of luid excreted by the kidneys. Two members of this receptor family that are present in the kidney—Olfr78, which was initially identified in the nose, and Gpr41, another seven-transmembrane receptor found in other cell types—are activated in response to short chain fatty acids produced by bacteria in the gut during digestion of fats or fiber.

To study the relationship between gut microbial-derived signals and kidney regulation of blood pressure, researchers administered the short chain fatty acid propionate to normal mice; they observed a rapid, but quickly reversible, drop in blood pressure. In subsequent studies, mice lacking the Olfr78 gene were observed to have lower baseline blood pressure than normal mice, and proprionate further lowered blood pressure in these mice. However, proprionate administration raised the blood pressure of mice lacking the Gpr41 gene, suggesting that the Gpr41 protein, when present, may respond to propionate by lowering blood pressure. Treatment with antibiotics, which disrupt normal gut function by killing intestinal bacteria, resulted in a significant increase in blood pressure in mice lacking the Olfr78 gene, but had no effect on blood pressure in normal mice. Together, these results suggest that the presence of gut microbes producing proprionate may play a role in the modulation of blood pressure in mice. This effect appears to be mediated, at least in part, by Olfr78 and Gpr41, which may work to balance one another to maintain normal blood pressure as proprionate levels in the blood luctuate in response to gut microbial metabolism. This discovery identifies a heretofore unknown connection between the gut, kidney, and cardiovascular systems. This connection may contribute to further understanding of high blood pressure and the future development of novel treatments.

Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory
receptor responding to gut microbiota-derived signals plays
a role in renin secretion and blood pressure regulation. Proc
Natl Acad Sci USA 110: 4410-4415, 2013.