Synthesis of N pi-methylhistamine and N alpha-methylhistamine by purified rabbit lung indolethylamine N-methyltransferase.
N tau-Methylhistamine is a major inactive metabolite of histamine and is formed by histamine N-methyltransferase (EC 2.1.1.8). However, a controversy exists concerning the presence of other N-methylated histamines, such as N pi- and N alpha-methylhistamine in mammalian tissues. Indolethylamine N-methyltransferase is present in mammalian tissues with the rabbit lung containing the highest concentration, but the physiologic function of this enzyme remains unclear. Using rabbit lung as a tissue source, we purified indolethylamine N-methyltransferase 260-fold and separated it completely from histamine N-methyltransferase. Histamine was a substrate for purified indolethylamine N-methyltransferase and unlike histamine N-methyltransferase which exclusively formed N tau-methylhistamine, indolethylamine N-methyltransferase catalyzed the in vitro formation of both N pi-methylhistamine and N alpha-methylhistamine. In contrast to histamine N-methyltransferase, indolethylamine N-methyltransferase activity was not inhibited by either high histamine concentrations or by quinacrine. Thus, mammalian tissues contain an enzyme capable of forming N pi-methylhistamine and N alpha-methylhistamine. This supports the concept of the existence of these compounds and suggests they may serve a physiologic function in mammals.
D000818:Animals; D006632:Histamine / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008745:Methylation; D008761:Methylhistamines / Q000096:biosynthesis*; D008780:Methyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits
D008761:Methylhistamines; C031205:3-methylhistamine; D006632:Histamine; D008780:Methyltransferases; C021439:indoleethylamine N-methyltransferase; D011796:Quinacrine