Biochemical identification of two types of phenamil binding sites associated with amiloride-sensitive sodium channels was written by Barbry, Pascal;Chassande, Olivier;Duval, Daniele;Rousseau, Bernard;Frelin, Christian;Lazdunski, Michel. And the article was included in Biochemistry in 1989.Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate This article mentions the following:
The biochem. basis for the existence of distinct forms of the epithelium Na+ channel that differ in their sensitivity to amiloride was analyzed by using phenamil, the most potent inhibitor known so far for the epithelium Na+ channel. [3H]Phenamil of high radioactive specific activity (30 Ci/mmol) was prepared and used to titrate [3H]phenamil-binding sites in pig kidney membranes. Kinetic experiments, equilibrium binding studies, and competition experiments indicated the presence in crude membrane preparations of 12 classes of independent binding sites. The 1st binding site was characterized by a high affinity for phenamil (dissociation constant 1 (Kd1) = 0.4 nM) and for amiloride (Kd1 = 0.1 μM). The 2nd binding site recognized phenamil and amiloride with lower affinities (Kd2(phenamil) = 28 nM, Kd2(amiloride) = 4 μM). The ratio of the resp. amounts of low- and high-affinity binding sites was 14 in different membrane preparations (range: 6-22). The 2 types of binding sites for [3H]phenamil copurified and were still observed after purification of the epithelium Na+ channel to homogeneity. Thus, â? types of pharmacol. distinguishable Na+ channels exist in the kidney. They correspond either to 2 isoforms of the apical Na+ channel or to 1 single type of channel under 2 different states of covalent regulation. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate).
Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazinesare six-membered aromatic heterocyclic organic compounds with two nitrogen atoms at 1,4-positions. Pyrazine is a weaker base (pKb = 13.4) than pyridine (pKb = 8.8), pyrimidine (pKb = 12.7). Pyrazines are chemical compounds (technically called âmethoxypyrazinesâ? found in grape skin and stems that are responsible for many âgreenâ?flavors in wine. Levels of pyrazines are dependent on viticultural practices, climate, and grape variety.Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate