Related Experiment Video

Updated: May 2, 2026

Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements
07:19

Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements

Published on: July 29, 2021

2.5K

In vitro inflammatory/anti-inflammatory effects of nitrate esters of purines

Loranne Maugé1, Theano Fotopoulou2, Stéphanie Delemasure3

  • 1INSERM U866, LPPCM, Faculté de Médecine, 7 bvd Jeanne d'Arc, 21000 Dijon, France; Cohiro Biotechnology, Faculté de Médecine, 7 bvd Jeanne d'Arc, 21000 Dijon, France.

European Journal of Pharmacology
|March 12, 2014
PubMed

Insights

The novel compound MK128, a purine analogue, effectively reduces inflammation by releasing nitric oxide (NO), inhibiting interleukin-1 beta (IL-1β) production in macrophages. MK128 demonstrates anti-inflammatory properties, unlike its derivative MK137.

Area of Science:

  • Immunology
  • Pharmacology
  • Biochemistry

Background:

  • Inflammation is a key process in many diseases.
  • Interleukin-1 beta (IL-1β) is a critical pro-inflammatory cytokine.
  • Nitric oxide (NO) plays a complex role in modulating inflammatory responses.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of novel purine analogues bearing a nitrate ester group.
  • To identify specific compounds that can inhibit IL-1β production in macrophages.
  • To elucidate the mechanism of action for potent anti-inflammatory compounds.

Main Methods:

  • Testing six purine analogues on human THP-1 macrophages and primary macrophages.
  • Measuring IL-1β production induced by ATP, H2O2, or LPS.
  • Assessing nitric oxide (NO) release and nitrite formation.
  • Evaluating the effects of NO scavengers and purinergic channel inhibitors.
  • Analyzing caspase-1 production.

Main Results:

  • Compound MK128 significantly inhibited ATP or H2O2-induced IL-1β production in macrophages.
  • MK128 was the only analogue to release NO, correlating with its anti-inflammatory effect.
  • The anti-inflammatory effect of MK128 was partially dependent on NO production.
  • MK137, lacking the nitrate ester group, exacerbated inflammation and acted as a purinergic receptor agonist.
  • MK128 reduced p20 caspase-1 production, suggesting inflammasome involvement.

Conclusions:

  • MK128 exhibits potent anti-inflammatory activity by inhibiting IL-1β production, likely through NO-mediated nitrosylation of inflammasome components.
  • The nitrate ester group is crucial for the anti-inflammatory action of these purine analogues.
  • MK137 acts as a pro-inflammatory agent by activating purinergic receptors and the inflammasome.
Keywords:
ATPCaspase-1H(2)O(2)Interleukin-1βNO donorTHP-1

More Related Videos

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds08:23

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Published on: February 16, 2022

4.4K
Analytical Techniques for Assaying Nitric Oxide Bioactivity11:28

Analytical Techniques for Assaying Nitric Oxide Bioactivity

Published on: June 18, 2012

17.7K

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.3K
Antianginal Drugs: Nitrates and β-Blockers01:16

Antianginal Drugs: Nitrates and β-Blockers

In cardiovascular health, antianginal drugs combat angina pectoris — a condition marked by chest pain owing to diminished blood flow to the heart.
Organic nitrates,  such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
1.9K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
3.9K
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
2.5K
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
613
Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents01:20

Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents

The gastric mucosa produces prostaglandins E2 (PGE2) and prostacyclin (PGI2), crucial in maintaining gastric health. They exert cytoprotective effects, including increasing bicarbonate secretion, releasing protective mucin, reducing gastric acid output, and preventing harmful vasoconstriction. These effects are mediated through various receptors, such as EP1, EP2, EP3, and EP4.
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
1.7K