Histamine: its metabolism and localization in mammary gland.

1. Mammary gland of mouse (Mus musculus), rat (Rattus rattus), guinea pig (Cavia porcellus), cow (Bos taurus) and pig (Sus scrofa) contains different but always high concentrations of histamine. 2.

Decreased histamine content and metabolism in mammary cancer tissue from C3H mice.

Histamine (HA) level and its metabolism in adenocarcinoma mammae, spontaneously growing cancer in C3H mice, were examined in relation to the type of tumor, intensity of tumor vascularization and the presence or absence of a secretory function. Histamine concentration being in mammary gland one of the highest among mammalian organs (418 nmol/g) was decreased by 90% in tumor (34 nmol/g). Similarly, histidine decarboxylase (HDC) activity dropped from approximately 7.

Histamine in C3H/W mice carrying spontaneous tumors of the mammary gland.

Adenocarcinoma mammae, a spontaneously growing mammary cancer in C3H/W mice, contrary to many transplanted tumors does not evoke any rise in histamine level either in the tumor or in distant tissues. On the other hand, the histamine level is reduced by 90% in the tumor in comparison with the healthy gland. This seems to be a consequence of the fall of histidine decarboxylase activity to below a detectable level.

Causal relationship between a tumour growth and the changes in histamine metabolism in tissues of sarcoma-bearing rat.

The relationship between malignancy and histamine metabolism in the liver and the small intestine has been examined in sarcoma-bearing Wistar rats two weeks after subcutaneous implantation of a transplantable methylcholanthrene sarcoma Sa1828 and on the 3, 7 and 14th days after tumour extirpation. Two weeks after tumour implantation, the histamine level was increased by 100% and 50% in the liver and the small intestine, respectively. On the 3rd day after extirpation of the tumour the level of histamine had returned to the control values and remained unchanged during the next 10 days.

Influence of pyridoxal 5'-phosphate on ethanol-induced changes in histamine catabolism in the guinea pig.

In guinea pigs, chronic intragastric administration of a 20% ethanol solution for 18 days (in increasing doses from 5 to 10 g/kg/day) leads, on the 18th day, to an enhancement of histamine level in the liver and the small intestine by up to 170% and 180% respectively. In these tissues the rate of histamine oxidative catabolism was depressed by about 20%. Histamine N-methyltransferase activity, as well as the level of acetylhistamine were not affected.

Histamine and its catabolism in tumour-bearing rat and mouse.

The hypothesis that failure of histamine (Hi)-mediated inter and intracellular cell-cell communication may be involved in the control of cellular growth has been tested in leukaemia-bearing mice and fibrosarcoma-bearing rats. In all examined tissues of mice bearing leukaemia L1210 cells and rats bearing methylcholanthrene fibrosarcoma histamine content was higher than in controls. Tissues of fibrosarcoma-bearing rats more intensively metabolized 14C-Hi and oxidative pathway was predominant.

In vivo formation of histamine phosphopyridoxal cyclic compounds.

A possibility of in vivo formation of cyclic compounds between histamine (Hi) given i.p. and endogenous pyridoxal (PL) or pyridoxal 5'-phosphate (PLP) has been studied.

Phosphopyridoxal cyclic compounds with histamine and histidine. 6: The formation of phosphopyridoxal cyclic compounds with histamine and histidine in the presence of biological material.

We have studied the dynamics of cyclic compound formation between histamine or histidine and pyridoxal 5'-phosphate (Hi-PLP or His-PLP) in incubates of rat gastric mucosa histidine decarboxylase (HD), rat intestinal diamine oxidase (DAO) or homogenates of either rat liver, intestine or gastric mucosa. For gastric mucosa HD, liver and gastric mucosa homogenates, the rate of cyclization was slightly decreased; however, the rate was significantly inhibited with intestinal DAO or intestinal homogenate. Binding of PLP by tissue components was measured; free PLP was bound abundantly by rat intestinal DAO and by rat intestinal homogenate.

Phosphopyridoxal cyclic compounds with histamine and histidine. 7: The properties of pyridoxal and phosphopyridoxal cyclic compounds with histamine and histidine.

Cyclic compounds synthesized from histamine (Hi) or histidine (His) with pyridoxal (PL)--[Hi-PL, His-PL] and Hi or His with pyridoxal 5'-phosphate (PLP)--[Hi-PLP, His-PLP] were tested for stability in buffer, acid and base solutions, crude homogenates of various tissues and in the presence of enzymes which metabolize Hi or His. The cyclic pyridoxal compounds were stable in all experimental conditions, whereas phosphopyridoxal cyclic products were degraded by rat intestinal DAO and rat intestine homogenate, apparently enzymatically. In acidic and basic solutions changes in migration velocity and u.

Conditions for the formation of cyclic compounds between pyridoxal phosphate and 5-hydroxytryptamine or 5-hydroxytryptophan.

5-Hydroxytryptamine (5HT) and 5-hydroxytryptophan (5HTP) form cyclic compounds (probably of the tetrahydro-beta-carboline type) with pyridoxal phosphate (PLP). In the first step of reaction a Schiff's base is formed; during incubation it is transformed into a cyclic compound with a maximum absorption spectrum at 330 nm. The degree of cyclization depends on pH and substrate concentrations.

Phosphopyridoxal complexes with histamine and histidine. (5) The kinetics of cyclic compound formation between histamine and pyridoxal-5'-phosphate in the presence of pig kidney diamine oxidase and rat intestinal histaminase.

Pig kidney diamine oxidase (DAO) and rat intestinal histaminase (Hi-ase) activities are inhibited in vitro by high concentrations of both a substrate (histamine) and a coenzyme (pyridoxal-5'-phosphate). This inhibition may be at least partially associated with the formation of a cyclic compound between histamine (Hi) and pyridoxal-5'-phosphate (PLP). The dynamics of this cyclic compound formation in the presence of both enzymes has been examined.

Phosphopyridoxal complexes with histamine and histidine. (4) The kinetics of complex formation between histidine and pyridoxal 5' -phosphate in the presence of bacterial histidine decarboxylase.

The dynamics of the complex formation between pyridoxal 5'-phosphate (PLP) and histidine in the presence of bacterial histidine decarboxylase was examined. Since PLP is able to form a cyclic product with histidine and histamine, the possibility of complex formation between PLP and histamine formed during a decarboxylation reaction was examined too. It was found that the cyclization reaction between PLP and histidine is equimolecular and the rate of cyclic product formation is not significantly influenced by the presence of enzyme.

Phosphopyridoxal complexes with histamine and histidine. (1) The kinetics of complex formation between pyridoxal 5'-phosphate and histamine.

Amines and amino acids are able to form cyclic compounds with pyridoxal 5'-phosphate (PLP). The quantitative relationship between histamine and PLP in the cyclization reaction were examined. It was found that one mole of amine reacts with one mole of coenzyme.

Phosphopyridoxal complexes with histamine and histidine. (3) The influence of presumed complex on activity of rat intestinal histaminase.

Histamine in high concentration inhibits the rat intestinal histaminase (diamine oxidase E.C. 1.