October 2010 - Nature riffs on its successful themes
and so it appears that the ability to “smell” may
not be unique to the nose. Jennifer Pluznick, an
assistant professor of physiology at Johns Hopkins,
has found that the odor-sensing proteins found in
the noses of mice also occur in their kidneys. The
same olfactory receptors may also exist in the human
nose, she says.
But could it be that the kidney is actually endowed
with a sense of smell?
Not exactly, says Pluznick. “It’s going too far to
say the kidney is smelling, although it’s kind of
fun to think of it that way.” She prefers the term
sniffing. “The kidney is sniffing the urine as it
goes by.”
February 2013- Researchers at The Johns Hopkins
University and Yale University have discovered that
a specialized receptor, normally found in the nose,
is also in blood vessels throughout the body,
sensing small molecules created by microbes that
line mammalian intestines, and responding to these
molecules by increasing blood pressure.
The finding suggests that gut bacteria are an
integral part of the body’s complex system for
maintaining a stable blood pressure.
“The contribution that gut microbes apparently make
to blood pressure regulation and human health is a
surprise,” says Jennifer Pluznick, Ph.D., assistant
professor of physiology at the Johns Hopkins
University School of Medicine. “There is still much
to learn about this mechanism, but we now know some
of the players and how they interact,” she adds.
Pluznick says that several years ago, thanks to a
“happy coincidence,” she found — in the kidney —
some of the same odor-sensing proteins that give the
nose its powers. Focusing on one of those proteins,
olfactory receptor 78 (Olfr78), her team
specifically located it in the major branches of the
kidney’s artery and in the smaller arterioles that
lead into the kidney’s filtering structures. Olfr78
also turned up in the walls of small blood vessels
throughout the body, she says, particularly in the
heart, diaphragm, skeletal muscle and skin.
To figure out which molecules bind and activate
Olfr78, the scientists programmed cells to have
Olfr78 protein receptors on their surface. They also
gave these same cells the ability to start a
light-producing chemical reaction whenever Olfr78 is
activated. By adding different cocktails of
molecules to the cells and measuring the light the
cells produced, they homed in on a single mixture
that activated Olfr78. They then tested each
component in that mix and found that only acetic
acid (a.k.a. vinegar) bound Olfr78 and caused the
reaction.
Acetic acid and its alter ego, acetate, are part of
a group of molecules known as short chain fatty
acids (SCFAs). When the team tested other molecules
in this group, they found that propionate, which is
similar to acetate, also binds Olfr78.
In the body of mammals, including humans, SCFAs are
made when zillions of bacteria lining the gut digest
starch and cellulose from plant-based foods. The
SCFAs are absorbed by the intestines into the blood
stream, where they can interact with Olfr78.
To pinpoint the effect of Olfr78, the scientists
gave SCFAs to mice missing the Olfr78 gene and found
that the rodents’ blood pressure decreased,
suggesting that SCFAs normally induce Olfr78 to
elevate blood pressure. However, when they gave
SCFAs to normal mice with intact Olfr78, they did
not see the expected increase in blood pressure, but
rather a decrease, though it was less pronounced
than before.
To test the effect of reducing the SCFAs available
to Olfr78, the team gave mice a three-week course of
antibiotics to wipe out the gut microbes responsible
for SCFA production. In this case, normal mice
showed very little change in blood pressure, but
mice without Olfr78 experienced an increase in blood
pressure, suggesting that there were other factors
involved in the Olfr78/SCFA/blood pressure
relationship.
The mystery was solved, Pluznick says, when the team
examined mice lacking Gpr41, a non-smell-related
protein receptor located in blood vessel walls that
also binds SCFAs. When SCFAs bind to Gpr41, blood
pressure is decreased. The researchers eventually
discovered that Olfr78 and Gpr41 both are activated
by SCFAs, but with contradictory effects. The
negative effect of Gpr41 is counterbalanced by the
positive effect of Olfr78, but Gpr41’s effect is
stronger, so an increase in SCFAs produces an
overall decrease in blood pressure.
“We don’t have the full story yet,” says Pluznick.
“There are many players involved in the maintenance
of stable levels of blood pressure, and these are
just a few of them. We don’t know why it would be
beneficial for blood pressure to decrease after
eating or why gut microbes would play a part in
signaling that change. But our work opens the door
for exploring the effects of antibiotic treatments,
probiotics and other dietary changes on blood
pressure levels in mice, and perhaps eventually
people.”
A description of the research, conducted in mice and
test tubes, appeared online Feb. 11 in the journal
Proceedings of the National Academy of Sciences.
[_private/vid/salute/Jennifer-Pluznick-smell-microbes.htm]
Other authors of the report include Ryan Protzko of
the Johns Hopkins University School of Medicine;
Jinah Han, La-Xiang Wan, Tong Wang, Anne Eichmann
and Michael Caplan of the Yale University School of
Medicine; Haykanush Gevorgyan, Arnold Sipos and
Janos Peti-Peterdi of the University of Southern
California; and others from the College de France,
Columbia University, the Washington University
School of Medicine and the University of Texas
Southwestern Medical Center.
This work was supported by grants from the National
Institute of Diabetes and Digestive and Kidney
Diseases (DK081610, DK64324, DK17433) and the Leducq
Foundation.
For more information
The Johns Hopkins Medicine
(MDN)
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