The author reflects on discoveries over the course of a century concerning histamine as a potent chemical signal and neurotransmitter, the development of antihistamines, including promethazine, and chlorpromazine from a common precursor, and the recognition of a major brain pathway involving histamine. Although chlorpromazine has been succeeded by numerous other antipsychotics, promethazine remains the antihistamine recommended for sedation in acutely disturbed patients, largely because it is potently anticholinergic at atropinic muscarinic receptors and therefore anti-Parkinsonian: this means it is also useful in combination with older antipsychotics such as haloperidol.

A Proficiency Test Scheme (PTS) for histamine analysis in fishery products using the Lerke and Bell (1976) fluorometric method was conducted in 26 different Moroccan laboratories. The goal of this PTS was to assess the abilities of a network of seven government laboratories and 19 laboratories performing auto-controls on fish processing units in Morocco. The samples used in the PTS were prepared from canned ground mackerel flesh, to which was added two significant concentrations (levels 1 and 2) of histamine. The homogeneity of the PTS samples was verified by a repeatability test and their stability by an intermediate fidelity test. The Cochran test was used to eradicate anomalous scattering and the Grubbs test to eradicate the anomalous averages observed in the results of the participating laboratories. The average and the usual deviations determined for levels 1 and 2 were used to calculate the Z-scores. For level 1 therefore, 23 out of 26 laboratories had satisfactory PTS results, and for level 2, 21 out of 26 laboratories had satisfactory PTS results. An analysis of the PTS samples using the HPLC reference method gave similar results for levels 1 and 2.

The histaminergic innervation of the thalamic dorsal and ventral lateral geniculate nuclei and the perigeniculate nucleus of the cat was examined immunohistochemically by means of an antibody to histamine.

We find histamine-immunoreactive neurons in the cat brain are concentrated in the ventrolateral portion of the posterior hypothalamus, confirming a previous report. However, this cell group also spreads into medial, dorsal, and extreme lateral regions of the posterior hypothalamus and extends as far rostral as the optic chiasm.

Histamine-labeled fibers cover all regions of the lateral geniculate complex, but the density of labeling varies. The ventral lateral geniculate nucleus (vLGN) is most densely labeled, the A laminae of the dorsal lateral geniculate are sparsely labeled, and the geniculate C laminae and the perigeniculate nucleus show intermediate amounts of label. Thus, histaminergic fibers demonstrate a predilection for zones innervated by the W-cell system. Labeled fibers exhibit few branchings and numerous en passant swellings, lending a beaded appearance. The vLGN showed more instances of fibers with larger-sized swellings (up to 2 μm).

Following injections of biotinylated tracers into the hypothalamus, we find labeled fibers throughout the lateral geniculate complex. The anterogradely labeled fibers resemblethe histaminergic fibers in morphology, distribution, and relative bouton size. Thus, the hypothalamus appears to be the source of the histaminergic fibers in the lateral geniculate complex.

Histamine-labeled fibers in the dorsal lateral geniculate nucleus (dLGN) exhibit uncommon ultrastructural morphology. Many extremely large, round, or elliptical vesicles fill the fiber swellings. Swellings are directly apposed to a variety of other dendritic and axonal profiles, but thus far no convincing synaptic contacts have been seen. The distribution and appearance of these histaminergic fibers resembles those reported for serotonergic fibers.

Our results support the idea that histamine works nonsynaptically as a neuromodulator in the lateral geniculate complex, affecting the level of visual arousal.

We tested the hypothesis that histamine is the transmitter released by barnacle photoreceptors. Median and lateral ocelli were incubated with 3H-histidine and found to synthesize 3H-histamine, identified by high-voltage electrophoresis. Synthesis could be blocked by the histidine decarboxylase inhibitor (S)-α-fluoromethylhistidine. Histamine was applied to 1-cells either by superfusion or by pressure ejection from a pipette (100 µM or 1 mM histamine) positioned close to the I-cell's soma. When bath-applied at concentrations ranging from 5–100 µM, histamine hyperpolarized the I-cell in a dose-dependent fashion and increased its conductance. At 100 µM, histamine abolished the I-cell's response to light. The response to a pulse of pressure-applied histamine was a hyperpolarization whose amplitude was graded with dose (determined by the duration of the pulse). This response persisted in concentrations of Co2+ and Cd2+ that blocked synaptic transmission from the photoreceptors. Cimetidine, an antagonist of mammalian H2 receptors, markedly decreased the cell's responses both to HA and to light at 100 µM and blocked both responses at 1 mM. Pyrilamine and triprolidine, H1 antagonists, had a complex effect on the I-cell's responses to histamine and to light. Neither H1 nor H2 antagonists, nor histamine itself, affected the voltage or light responses recorded in the presynaptic terminal region, or any phase of calcium-dependent action potentials induced in the terminal in the presence of tetraethylammonium ion. Thus, biochemical, immunocytochemical, and physiological evidence suggests that HA is the transmitter from these photoreceptors to the I-cells. Although gammaaminobutyric acid (GABA) is also present in the photoreceptors, it did not affect the I-cell's responses to light or to histamine when bath-applied at 100 µM. Thus, GABA does not appear to modulate transmission from the photoreceptor to the I-cell.

Biochemical evidence indicates that GABA and histamine may both be synthesized by barnacle photoreceptors (Koike & Tsuda, 1980; Timpe & Stuart, 1984; Callaway & Stuart, 1989b). We used antisera against GABA- and histamine-protein conjugates to determine whether the photoreceptors contain either or both of these antigens. Both antisera labeled all of the photoreceptors in each of the three ocelli. Histamine-like immunoreactivity was found throughout each photoreceptor cell but was most intense at their presynaptic terminals. Histamine-like immunoreactivity was blocked by preincubation of the antibody either with histamine or with a histamine-protein conjugate. GABA-like immunoreactivity was found in all parts of the photoreceptors including the cell body, axon, rhabdomeric dendrites, and presynaptic terminals. GABA-protein conjugates blocked the GABA-like labeling of the photoreceptors, while protein conjugates with histamine, L-glutamate, L-glutamine, β-alanine, and taurine did not. Histamine-like immunoreactivity in the supraesophageal ganglion was confined to the photoreceptor terminals and a second, loose plexus of endings in the main neuropil. GABA-like immunoreactivity, in contrast, was found in approximately twenty-five pairs of neurons of this ganglion. In the cirral nerves, which are expected to contain inhibitory motoneurons, unidentified axons also labeled with the GABA antiserum.

The contractile response of smooth muscles to spasmogens can be divided into two components by modifying the extracellular Ca2+ concentration. The phasic component depends on the mobilization of Ca2+ from intracellular stores whereas the tonic component depends, to a large extent, on the influx of extracellular Ca2+. The present study was designed to investigate the effect of ketamine on the tonic response to carbachol or histamine in the guinea pig trachea. Tracheal spirals from female guinea pigs were mounted in organ baths filled with aerated physiological buffer, and their isometric tension was measured. The phasic response to 10−7m carbachol or 10−5m histamine in Ca2+ -free, ethylene glycol-bis(β-aminoethyl ether)-N, N,N',N'-tetraacetic acid-containing buffer and the tonic response to each spasmogen after restoring [Ca2+] in the buffer was measured in the absence or presence of ketamine. In the presence of normal physiological buffer, ketamine decreased the contractions induced by carbachol or histamine in a dose-dependent fashion. No measurable phasic response to either carbachol or histamine was obtained in our preparation. Ketamine (5 × 10−5m−10−3m) reduced the tonic response to 10−7m carbachol to 79.5±2.7−4.3±0.7% of the response without ketamine. Similarly, ketamine (5 × 10−4m−2 × 10−3m) decreased the tonic response to 10−5m histamine to 80.7±3.9−23.0±3.2% of the response in the absence of ketamine. Our findings support the hypothesis that ketamine inhibits the paracrine agent-induced contractions of smooth muscles by interfering with the influx of extracellular Ca2+ or with an intracellular event(s) requiring extracellular Ca2+.

Atracurium causes a decrease in systemic vascular resistance (SVR) and mean arterial blood pressure (MAP) which has been ascribed to histamine release. However, histamine receptor blockade does not prevent these decreases completely. The hypotensive side effects of atracurium may not only be caused by histamine. In this study we examined the vasoactive effects of atracurium with and without histamine receptor blockade in an isolated femoral artery preparation of the rabbit. We also investigated whether vasodilatation caused by atracurium depends on the presence of endothelial cells. Tyrode perfused, rabbit femoral arteries were constricted with noradrenaline (NA) to ±70% of their passive diameter. Endothelial function was checked with acetylcholine (ACh). The vessels were divided into two groups. In both groups the responses to histamine (1.0−10−6m) and atracurium (3.2−10−5m) were determined. In group one (n = 5), the histamine and atracurium responses were repeated during histamine receptor blockade. In group two (n = 5), the diameter responses to histamine and atracurium before and after endothelium removal were compared. Also, some vessel segments (n = 5) were histologically prepared and examined for mast cells. The vasodilatory responses to atracurium both with and without histamine receptor blockade were the same. Removal of endothelium caused an increase in the histamine response, while the dilating response to atracurium remained constant. We conclude that in the isolated femoral artery of the rabbit, atracurium induces vasodilatation that is not mediated by histamine release and cannot be prevented with histamine receptor blockade. The mechanism of atracurium induced dilation is independent of the endothelium and is located in the smooth muscle cell.