C. Maśliński

Histamine and its metabolism in mammals part I: Chemistry and formation of histamine

Several important reviews dealing with histamine have appeared in recent years, covering specific problems such as histamine synthesis, catabolism, transport, storage, and role in physiological and pathological phenomena. However, interest in biogenic amines, histamine included, has increased to a great extent; experiments are performed so rapidly that every year hundreds of publications appear. This is not surprising in view of the role of these compounds as regulators of homeostasis, i.e., factors responsible for maintenance of many functions of living organisms. Hence the obvious usefulness of periodic reviews of what has been published but not always commonly accepted, and of the problems that require either confirmation or disproval to make the research clearer and more precise and to fill the voids with knowledge. For these reasons it seems worthwhile to examine the history of histamine research before proceeding with a survey of the present state of the research itself. The attempt to systematize past work often proves to be very useful. Obviously, every systematization means simplification, and scientific phenomena are, in reality, always richer than is apparent following artificial systematization. Nevertheless, the gain achieved by classification and systematization is usually greater than the loss caused by simplification. Since histamine was synthesized by Windaus and Vogt in 1907, or, to be more precise, since the fundamental work of Dale and Laidlaw beginning in 1910, histamine research has passed through various stages. The initial period, the longest as it lasted for almost 50 years, may be defined as the period of the pharmacology of histamine. It provided the foundations for research on the pharmacodynamic action of histamine. The action of histamine on blood vessels, heart, microvascular permeability, smooth muscle and gastric secretion were discovered. Much was explained on the role of histamine as one of the mediators of the acute inflammatory reaction, the immediate allergic reaction and as the factor responsible for a number of the symptoms of anaphylaxis. Some data suggesting a role for histamine as a mediator of nervous activity appeared. It should be stressed that a very important portion of the contemporary data concerning histamine and its action originated during that period, yet the physiological role of histamine has not been made clear up to now. The pharmacological data pointed the way to some particular lines of research; many of them proved to be of great use in the attempts to elucidate the physiological role of histamine. Yet it is also true that they brought about premature conclusions on the physiological role of histamine, and thus led research along paths to nowhere. A critical analysis of the pharmacological approach to the role of histamine has led Kahlson

Does histamine interact with cholinergic neurones in its cataleptogenic action in the rat

Abstract Histamine, injected directly into the lateral ventricle of the rat brain, produced hypokinesia and akinesia, the effect being dependent on the dose. Histamine-induced catalepsy was antagonized by chloropyramine, diphenhydramine and mepyramine, blockers of H1-histamine receptors, while cimetidine and metiamide, blockers of H2-histamine receptors, showed no discernible influence. Amodiaquine, an effective in vivo inhibitor of histamine catabolism in brain (amodiaquine inhibited HMT activity in particular structures of rat brain by approximately 70%), significantly potentiate and prolonged histamine-mduced catalepsy. Pretreatment of rats with amphetamine, apomorphine or scopolamine prevented post-histamine catalepsy. Histamine, in a catalepsy-producing dose, had no apparent effect on either amphetamine-, or apomorphine-induced stereotypy in rats. The mechanism of histamineinduced catalepsy is discussed with regard to its possible interaction with acetylcholine- and dopaminecontaining neurones in brain.

The mechanism of the inhibitory action of zinc on histamine release from mast cells by compound 48-80,.

peritoneal mast cells, and in vivo on passively sensitized rat skin. Homocytotropic antibodies were produced in F1 hybrids of August and Wistar rats after immunization with 500 [zg of egg albumin in 1 ml of aluminium hydroxide gel (60 mg AI(OH)3 per ml) given subcutaneously into the back and into the foot-pads. The sensitizing antibodies, detectable in serum after 7-8 days (PCA titre 1:40-1:160) have properties of the IgE class of immunoglobulins. The peritoneal mast cells of actively sensitized rats released histamine when exposed to egg albumin in vitro at 37~ Nicotinamide, 10 z M, preincubated with peritoneal mast cells for 15 minutes before challenge, inhibited spontaneous, and antigeninduced, histamine release; at 4 x 10-z M, inhibition was complete. 60% of inhibition was obtained in 1 minute of preincubation. Increasing incubation time to 10 or 15 minutes produced complete inhibition. In vivo the homologous PCA reaction was produced in Wistar rats with antiserum in dilutions 1 : 20, 1 : 40 and 1 : 80; reaction intensity was determined by Evans blue extraction with formamide. Nicotinamide in i.p. doses of 100 and 200 mg/kg, 30 minutes before challenge with antigen, reduced the PCA reaction 15-45% (antiserum dilution 1:20); 200 mg/kg i.v. 10 minutes before antigen provoked a 25% reduction of PCA (antiserum dilution 1:20). In all cases the per cent of PCA inhibition was higher in antiserum dilution 1:40 and reached 100% in dilution 1:80. It is evident that nicotinamide inhibits the rat anaphylactic reaction both in vivo and in vitro, but high doses are required. Nicotinamide, 5--40 m M is a potent inhibitor of cAMP phosphodiesterase in vitro [4]. Possibly our high concentrations of nicotinamide were required for influencing intracellular levels of cAMP through inhibition of phosphodiesterase activity.

An interaction of histamine H2-receptor antagonists with the noradrenergic system in rat brain

Intraventricular administration of 50 microgram of burimamide or 250 microgram of either metiamide or cimetidine decreased the NA concentration in rat hypothalamus by nearly 30%. Cimetidine did not significantly influence either DA or DOPAC levels in striatum. Cimetidine and metiamide significantly potentiated locomotor activity of tranylcypromine-treated rats and this effect was antagonized by phentolamine. It is concluded that the three histamine H2-receptor antagonists released NA in rat brain.

Participation of aldehyde dehydrogenase in the oxidative deamination pathway of histamine and putrescine

Some guinea pig tissue homogenates have shown the ability to catabolize,in vitro, imidazoloacetaldehyde (ImAAL) and gamma-aminobutyraldehyde (GABAL) via NAD-dependent aldehyde dehydrogenase (ALDH, EC 1.2.1.3). The liver, kidney, small intestine and gastric mucosa are the richest sources of ALDH activity towards ImAAL. The liver, kidney, small intestine and pancreas also show ALDH activity with GABAL as a substrate. All tissues tested have shown low Km and high Km ALDH activity with propionaldehyde as substrate. The guinea pig liver ALDH which is able to oxidize ImAAL and GABAL is located exclusively in the cytoplasm.

Diamine oxidase activity and imidazoleacetic acid formation in the foetal and maternal guinea pig liver

Diamine oxidase activity and imidazoleacetic acid formation in the foetal and maternal guinea pig liver during gestation were examined. DAO activity and IMAA formation in the foetal liver increased continuously, while maternal enzyme activity and ImAA formation in the second half of pregnancy simultaneously decreased. The roles of GABA and ImAA are discussed.

The response of histamine degrading enzymes to nematode infection.

The response of intestinal mucosal enzymes which metabolize histamine i.e. diamine oxidase (DAO), histamine N-methyltransferase (HMT), and monoamine oxidase (MAO), to infection withNippostrongylus brasiliensis has been examined in mice and compared to the changes evoked byin vivo administration of compound 48/80. Infection with the parasite resulted in a significant decrease in the concentration of both amine oxidases, followed by recovery of MAO and an overshoot in DAO activity. HMT activity was enhanced at the beginning of infection, then decreased markedly by days 11 to 15, and sharply increased thereafter. Histamine levels were on average only 20% higher than the basal levels over the entire period studied, except on day 4 when they were slightly reduced. Histamine is alleged to be a potential inducing factor for degrading enzymes. Consistently, the histamine releaser 48/80 significantly elevated intestinal mucosal DAO and in some of the mice also increased HMT activity.

Histamine level and transglutaminase activity may provide indication of the development of spontaneous mammary tumor in C3H mice

Histamine (HA) concentrations and HA metabolizing enzyme activities were measured in macroscopically unchanged mammary glands and in tumor tissue of C3H mice carrying spontaneous mammary tumor as well as im mammary glands of control subjects matched for age.The great fall in HA level and the enzyme activities in tumor tissue was confirmed. In host mammary glands which showed no current evidence of neoplasm, consistently lower than normal HA concentrations and elevated transglutaminase (TG) activity were found, It is suggested, therefore, that HA level and TG activity may provide an early indication of the development of spontaneous mammary tumor.

The participation of H1 and H2 histamine receptors in vascular skin permeability induced by some imidazoles

ConclusionsThe inhibitory action of both types of histamine receptor antagonists on imidazole-induced skin vascular permeability suggests that histamine receptors are involved in this phenomenon.The mechanism of the action of imidazoles on skin vessels may be related to the endogenously released histamine [7] which subsequently stimulates its receptors and/or directs stimulation by imidazoles of both types of histamine receptors present in the vascular tree.

The pharmacological inhibition of the heterologous PCA reaction by histamine antagonists and chloropromazine

ConclusionThe experiments with the passive sensitization of rat skin by mouse IgE show that this heterologous PCA reaction may be modulated (similarly to homologous reaction) by antihistaminic and antiserotonic drugs. It supports the concept of a role of both histamine and serotonin in rat and mouse anaphylaxis.