New Insights into Autacoids in Disease

Dear Colleagues,

Research on autacoids such as prostaglandins, thromboxanes, leukotrienes, serotonin, endothelin, angiotensin, histamine, and bradykinin has been active in recent years, and new discoveries have been reported in various fields. New findings regarding autacoids and related proteins, which have been attracting attention in recent years, are reported below.

1. Autocoids and immunity

It has become clear that autacoids play an important role in regulating immune system function. For example, prostaglandin E₂ has been shown to inhibit immune cell activation and suppress inflammatory responses. In addition, angiotensin and bradykinin elicit an increased immune response, which may hold great promise for therapeutic manipulation to boost the immune response against a variety of stimuli, including infections and tumors. Further research is underway on angiotensin-converting enzyme (ACE) 2 and the mechanisms of COVID-19 virus entry, ACE inhibitors and the risk of severe disease in COVID-19 patients, and ACE inhibitors and COVID-19 vaccination. On the other hand, thromboxane A₂ has been shown to promote immune cell activation and play an important role in infection defense.

2. Autocoids and metabolism

Autocoids have also been suggested to be involved in energy metabolism and lipid metabolism. For example, drugs that suppress the action of angiotensin II have been shown to be effective in treating diabetes and lipid metabolism disorders. Bradykinin has also been shown to promote the activation of Akt, a key enzyme involved in insulin signaling. Lipoxin A4 has also been shown to be effective in lowering blood sugar levels.

3. Autocoids and nerves

Autocoids have also been shown to affect neuronal function. For example, endocannabinoids have been shown to enhance the function of brain regions that are involved in memory and learning. Serotonin is known as a neurotransmitter that is involved in mood regulation. However, in recent years, it has become clear that serotonin plays a variety of important roles, including influencing appetite, sleep, memory, learning, bone density, and immune function. Prostaglandin D₂ has also been shown to have protective effects on neuronal cells.

4. Autocoids and cancer

Autocoids have been shown to be involved in cancer cell proliferation, invasion, and metastasis. For example, prostaglandin E₂ has been shown to promote cancer cell proliferation and metastasis. On the other hand, lipoxin A₄ has been shown to be effective in inducing cancer cell death.

5. Autacoids and aging

It has been shown that the amount of autacoids that are produced changes with aging. For example, the production of prostaglandin E₂ has been shown to decrease in older adults, which may be associated with inflammation and cognitive decline in older adults.

These new findings suggest that autacoids are involved in various diseases and are expected to lead to the development of new treatments targeting autocoids.

6. Blood pressure regulation and heart function

There are autacoids that have vasodilatory and constrictive effects (angiotensin, endothelin, bradykinin, nitric oxide, etc.) and play an important role in regulating blood pressure. Autacoids also have the effect of regulating myocardial contractility, heart rate, and myocardial blood flow. In recent years, it has become clear that autacoids are involved in blood pressure regulation and the onset and progression of cardiovascular diseases such as heart failure and arrhythmia.

7. Angiogenesis

Autocoid has the effect of promoting blood vessel formation and is expected to be useful in the treatment of ischemic heart disease and lower limb ischemia. For example, vascular endothelial growth factor has the effect of promoting autacoid production and promoting angiogenesis. In recent years, new treatments targeting autocoids have been developed.

Future issues in autocoid research:

Research on autacoids has become more active in recent years, but there are still numerous unknown factors. Future challenges include the following:

• Further elucidation of the mechanism of autocoid biosynthesis and degradation.
• Elucidation of how autacoids act on specific cells and tissues.
• Development of new treatments targeting autocoids.

By overcoming these challenges, we hope to deepen our understanding of autacoids and help develop treatments for various diseases.

In this Special Issue, we are soliciting a wide range of physiological, pharmacological, pathological, and biochemical reports on new findings regarding autacoids and diseases.

Yours faithfully,

Prof. Dr. Katsutoshi Yayama
Guest Editor

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• angiotensin
• bradykinin
• endothelin
• prostaglandins
• thromboxanes
• leukotrienes
• serotonin
• histamine
• angiotensin-converting enzyme
• angiotensin receptor
• renin
• kininogen
• kallikrein
• cyclooxygenase
• phospholipase A₂