IN VIVO FORMATION AND CATABOLISM OF [¹⁴C]HISTAMINE IN MOUSE BRAIN

Abstract

Abstract— The formation of histamine in brain was studied in mice injected with l‐[14C]‐histidine (ring 2‐14C) intravenously (i.v.) or intracerebrally; [14C]histamine appeared rapidly and exhibited a rapid rate of turnover. Drugs known to block various pathways of histamine catabolism were tested for effects on brain–[14C]histamine and [14C]‐methyl‐histamine in mice given (1) [14C]histamine i.v., (2) [14C]histamine intracerebrally, and (3) l‐[14C]histidine i.v. Blood‐borne histamine did not enter brain; brain histamine was formed locally by decarboxylation of histidine Methylhistamine did cross the blood‐brain barrier. Methylation was the major route of histamine catabolism in mouse brain and some of the methylhistamine formed was destroyed by monoamine oxidase. No evidence for catabolism by the action of diamine oxidase was found.

Direct Evidence for Increased Continuous Histamine Release in the Striatum of Conscious Freely Moving Rats Produced by Middle Cerebral Artery Occlusion

“…There is no high-affinity uptake of HA in the brain, and the HA released from nerve terminals is predominantly methylated by HA N-methyltransferase to tele methylhistamine (Schwartz et aI., 1971;Schayer and Reilly, 1973). Therefore, the increased HA out put in MCA-occluded rats may be due to facilitation of HA release and/or inhibition of HA N-methyl transferase.…”

9-Amino-1,2,3,4-Tetrahydroacridine Is a Potent Inhibitor of Histamine N-Methyltransferase.

“…In the mammalian brain, however, the methylation is the exclusive route of histamine metabolism (26,27). HMT is inhibited by several centrally-acting drugs such as chlorpromazine, imipramine and H1 receptor antagonists, although their potencies are low (12,28,29).…”

Altered Methylprednisolone Pharmacodynamics in Healthy Subjects With Histamine N‐Methyltransferase C314T Genetic Polymorphism

“…The circadian baseline cortisol concentrations can be approximated by the sum of a Fourier series of N harmonics 18 : (4) where T is the period and the constants a 0 , a n , and b n , with n = 1,2, … are the Fourier coefficients of the function Cort(t). The bracketed term is referred to as the nth harmonic.…”

“…2 Histamine N-methyltransferase catalyzes the N-methylation of histamine, which was suggested to be the major significant pathway for the biotransformation of histamine in bronchial epithelium and the brain. [3][4][5] Interindividual variation of HNMT activity has been demonstrated in whites and Han Chinese. 6,7 This variability can be explained in part by a C to T transition at nucleotide 314 (exon 4) of the HNMT gene, causing an amino acid change of threonine to isoleucine at codon 115, which results in low immunoreactive HNMT protein and activity.…”