The basis of this study was the assumption that mast cells can take up tele-methylhistamine (MeHi), as is known for other biogenic amines. The influence of extracellular MeHi on its uptake (active or passive) in isolated rat mast cells and in different rat tissues was studied in vitro. Rat peritoneal mast cells were incubated for 15 or 30 min at 37 or 1 degree C with different concentrations of MeHi. Submandibular gland, skeletal muscle, lung and heart of the rat (200-500 mg of each) were chopped and incubated for 20 min at 37 or 1 degrees C in buffer containing MeHi. Histamine (Hi) and MeHi in the cells and in the tissues were then determined by HPLC assay. Mast cells were capable of taking up MeHi in a time- and dose-dependent manner. MeHi levels increased from 5-10 ng per ml of incubated cell suspension (control) to 60-100 ng/ml after 15 min incubation. It can be assumed that the accumulation of MeHi in mast cells is due to a simple diffusion process since no significant change was noticed at 1 degree C. The preincubation of the cells with serotonin reduced MeHi accumulation, thus indicating MeHi competes with the same binding sites in mast cells as Hi and serotonin. Tissues showed high capacity for MeHi accumulation and MeHi surmounted endogenous Hi levels. Uptake was reduced at 1 degree C, yet the accumulation of MeHi was still high. The results indicate that mast cells can take up a smaller portion of free MeHi and they can have a function in its micro-regulation whereas other tissue cells have a predominant role in the removal of free MeHi from the blood.
Effects of the antidepressant drug mirtazapine on plasma levels and on the kinetics of injected histamine were studied in the cat. In the dose of 0.6 mg/kg mirtazapine did not affect the characteristics of the elimination curve of histamine. The higher dose of mirtazapine (1.2 mg/kg) prevented the increase of plasma histamine levels.
Rat peritoneal cells were used to study the uptake of tele-methylhistamine (MeHi) from the incubation medium. The cells obtained from the peritoneal cavity were concentrated five times. MeHi in the cells was measured using an HPLC-assay with fluorescence detection. After the incubation of the cells in a buffer medium containing different concentrations of MeHi, a significant increase in MeHi content within the cell fraction was found. The increase was dose- and time-dependent. Preincubation with compound 48/80 did not affect the uptake of MeHi by the cells. The results indicate that MeHi may be taken up by mast cells.
Histamine release in the rat was induced in vivo either by a single dose of compound 48/80 injected i.v. or by four repeated, daily doses of the same compound injected i.p. After i.v. injection the levels of blood histamine were determined and after i.p. injections the changes in both tele-methylhistamine and histamine levels in different tissues were investigated. I.v. injection of 48/80 induced a very rapid and marked increase of blood histamine by 7.4 to 11-fold over the control levels within the first two minutes. After repeated i.p. injections of compound 48/80 most tissues showed higher than normal tele-methylhistamine/histamine ratios. The results suggest that agents known to induce release of histamine from mast cells may exert significant changes in blood and tissue histamine levels and that liberated histamine is thereafter extensively catabolized.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.