Mise en évidence in vitro de la biosynthèse d'histamine à partir de carnosine par le rein de souris gravide

Abstract

Kidneys of pregnant mice synthesize histamine when incubated in the presence of carnosine, manganese, and pyridoxal phosphate. Intensity of biosynthesis increases linearly with the amount of enzyme and the incubation time. The reaction can only be catalysed by two enzymes that are located in kidneys and act in succession: carnosinase, which hydrolyzes carnosine into its two moieties, and histidine decarboxylase, which transforms histidine, a product of carnosine degradation, into histamine. The biosynthesis of histamine from carnosine seems to increase with the progress of pregnancy. In nonpregnant mice, kidneys do not effect this biosynthesis. The above results directly demonstrate that carnosine may be used for histamine synthesis when the activity of histidine decarboxylase is high, as in pregnant mouse kidney. Vertebrate carnosine, its role still enigmatic, might thus be mainly a potential histidine reservoir that would be mobilized any time there is a significant requirement for histidine, such as for histamine biosynthesis.

The distribution of carnosine and related dipeptides in rat and human tissues

“…However, our immunohistochemical assay did not detect carnosine or related compounds in rat kidney. Arnould [17] showed that an extract of pregnant mouse kidney converted added carnosine into histamine, however the kidney was not assayed for endogenous carnosine.…”

Mobilization of Renal Carnosine and Histidine to Histamine during Compound-48/80-Induced Shock

“…Arnould [17] identified carnosine in the kidneys of pregnant mice and documented increased activity of the histamine-synthesizing enzyme histidine decarboxylase as pregnancy progressed, and Cianciaruso et al [18] de monstrated that the dog kidney takes up carnosine and releases histidine regardless of the type of diet (histidinefree versus histidine-replete) being provided. Others, such as Abboud et al [19], have noted an increase in histamine synthesis in kidneys of rats treated with puromycin to cause nephrosis.…”

“…Earlier work from this laboratory [9 15] and others [16][17][18] has clearly de monstrated a link between carnosine, free histidine and histamine synthesis following surgical trauma, infection, femur fracture, wounding, pharmacologic stress and pregnancy. These studies support our hypothesis that carnosine serves as a non-mast cell histidine reservoir available for histamine synthesis following trauma or stress.…”

“…Histamine is known to occur in relatively high concentrations in renal tissue of several species [17][18][19][20][21][22] and has been demonstrated to exert vasodilatory effects, predominantly at the preglomerular, but also at the postglomerular capillary sphincters [22 26]. Other studies [22,26,27] have demonstrated that histamine causes an accumulation of cyclic AMP in the glomeruli which may be responsible for altering the con tractile properties of mesangial cells, thus changing renal blood How and glomerular filtration properties, implicat ing histamine in renal blood flow and glomerular filtra tion autoregulation.…”

“…Other studies [22,26,27] have demonstrated that histamine causes an accumulation of cyclic AMP in the glomeruli which may be responsible for altering the con tractile properties of mesangial cells, thus changing renal blood How and glomerular filtration properties, implicat ing histamine in renal blood flow and glomerular filtra tion autoregulation. It has been previously shown that carnosine exists in the kidney and may act as a reservoir for histidine which is mobilized to histamine to meet the increased requirements of pregnancy [17]. Cianciaruso et al [18] have also shown in dogs (for whom histidine is an essential amino acid) that intravenous infusion of carno sine results in net renal uptake of carnosine and release of histidine, an effect which was independent of the histi dine content of the diet (histidine-free versus histidinereplete).…”