The body's own cannabinoids widen the bronchi

The bronchi are dilated by the body's own cannabinoids

Obstructive pulmonary disease is the third most common cause of
death in the world.
They include chronic obstructive pulmonary disease (COPD) and bronchial asthma
, which affect many smokers.
During an asthma attack, the bronchi contract so much that it is impossible to breathe out anymore – which can be life-threatening
.
"Asthma is an inflammatory process, but fatal is bronchoconstriction," explains
Annika Simon, lead author of the study.
"That's why we're so interested in
the regulation of this contraction.
"

In a previous study, researchers similarly focused on the body's own cannabinoid system, specifically its role in the blood vessels in
the lungs.
The most well-known endocannabinoid is cannabinamide
.
Daniela Wenzel explains: "Since our findings show that Nandaramide dilates the bronchi, we wanted to understand the exact mechanism
behind it.
"

Enzymes degrade cannabinoids

It soon became clear that two of the best-known amide receptors (CB1 and CB2) were not associated
with this regulation.
Therefore, there must be another signaling pathway through which the messenger substance Nandaramide acts on the bronchi
.

Daniela Wenzel and her team demonstrated that this alternative pathway uses an enzyme
called fatty acid amide hydrolase (FAAH).
FAAH degrades amides to produce arachidonic acid, which in turn is converted to prostaglandin E2
.
"We know that prostaglandin E2 can dilate the bronchi," Annika Simon noted
.
Prostaglandin E2 acts through certain receptors, leading to an increase in
the messenger substance cAMP (cyclic adenosine monophosphate).
Daniela Wenzel said: "The inhaled drugs that have been established to treat asthma are aimed at exactly this – the increase
in cAMP.
" So, the goal is the same, but the path is different
.

Amide deficiency in asthma

Wenzel and her team gradually deciphered the signaling pathway
.
They found that the FAAH enzyme is located in
bronchial smooth muscle and ciliated epithelium.
An increase
in cAMP after amide administration was detectable in both mouse models and human bronchial cells.
To find out whether anandamide could also work in asthma patients, the team used a disease model in mice in which certain substances could be used to create artificial asthma
.
In these animals, administration of anadaramide also causes bronchiectasis
.
"This means that asthma does not lead to drug resistance to anandamide," explains
Daniela Wenzel.
In addition, the researchers found that asthmatic animals had fewer anandamide and other endocannabinoids
in their bronchial systems compared to healthy animals.
"Therefore, this amide deficiency may be one of the causes of bronchial asthma," concludes
Daniela Wenzel.

The discovery of new signaling pathways also opens up new possibilities
for intervening in disease processes.
"But there is still a long way to go, it will definitely take a few years
," stressed Daniela Wenzel.
She explicitly warned patients not to experiment
with cannabis plants.
"We cannot draw any direct conclusions
about phytocannabinoids from the discovery of endocannabinoids.
In addition to known cannabinoids, it is completely unclear
what other components can be found in the cannabis plant.
In addition, these plants sometimes contain harmful substances
.
"Still, the study's findings already point to a better understanding of the body's own cannabinoid system, which could lead to new treatment options
for lung diseases within a few years.
"