The effect of substance P and compound 48/80 on histamine and serotonin release from not isolated and isolated mast cells have been compared in experiments in vitro. The response of not isolated and isolated mast cells were virtually identical. The release of both amines, in response to 48/80 and substance P, was dose-dependent. The percentage of histamine released by 48/80 was significantly higher than the percentage of serotonin, the difference being higher at lower concentrations of compound 48/80 after 15 min of incubation. Substance P also showed a tendency to higher efficiency for histamine than for serotonin release. In contrast to 48/80, the dose-response curves for histamine and serotonin release were parallel. These results support the view that the ratio between histamine and serotonin release depends on the liberator used. They also showed that this ratio can depend on the concentration of the agent inducing secretion. The results indicate that substance P as well as 48/80 act rather selectively as histamine liberators and that there is some difference in releasing properties of 48/80 and substance P.

It can be suggested that pyrethroids inhibit signal transduction in human lymphocytes ex vivo, and do not act via lymphocyte-influencing histamine release.

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Characteristics of histamine (Hi) and 5-hydroxytryptamine (5-HT) release from rat peritoneal mast cells in response to the polypeptide adrenocorticotropin (ACTH) were studied. During a 15 min incubation at 37 degrees C, ACTH evoked Hi as well as 5-HT release from rat mast cells at concentrations of 1 X 10(-4) M-1 X 10(-3) M. The release was dose-dependent and very rapid. After 15 sec the amount of the amines released was the same as after 4.5 min. In most experiments, the percentage of Hi release was slightly but significantly higher than the percentage of 5-HT release. Hi and 5-HT release induced by ACTH also took place in a calcium-free medium. However, the release of the amines was decreased when calcium was omitted. Comparison of the effects of ACTH, compound 48/80 and substance P on mast cell secretion showed that ACTH is about 100 times less active then substance P which was in turn about 100 times less active than compound 48/80. When both ACTH and compound 48/80 were used together as liberators , the release was significantly higher than with either liberator alone. Our results indicate that there are receptor sites for the endogenous polypeptide ACTH on the mast cell membrane which mediate Hi and 5-HT release. This release was found to resemble that evoked by the basic secretogogue compound 48/80 but in some aspects to be different from that evoked by substance P.

IntroductionExogenous histamine, acting peripherally via H 1 and H 2 receptors, produces a decrease in mean arterial pressure (MAP). Similarly, administration of compound 48/80, which increases a release of endogenous histamine from mast cells, leads to circulatory depression and occurrence of ventricular arrhythmias in rats [1]. Previous studies demonstrate that plasma histamine concentrations, after injection of compound 48/80, can be lowered by pre-treatment with tricyclic antidepressants in rats [2]. Moreover, amitriptyline (AMI) and mirtazapine treatment also reduces peak plasma histamine level, which follows an intravenous (i. v.) administration of histamine in rats [3] and cats [4], respectively. In this study we examined cardiovascular responses and changes in plasma histamine concentrations after i. v. histamine injection in rats pre-treated with AMI and citalopram (CIT) which are representatives of two different classes of antidepressants. Materials and methodsStudies were carried out in male Wistar rats anaesthetised with ethylurethane (1.25 g/kg intraperitoneally [i. p.]) weighing 230 -260 g in accordance with EU directives. Arterial pressure and heart rate (HR) were measured using the pressure transducer RMN-201 (Temed, Inflamm. res. 53, Supplement 1 (2004) S97-S98 Poland) and the electrocardiograph Diascope 2 (Unitra Biazet, Poland), respectively [5,6]. The animals (n = 6) were treated i. v. with histamine (10 mg/kg) 15 min or 1 h after i.p. pre-treatment with AMI (2.7 mg/kg), CIT (1 mg/kg) or saline (0.5 ml). In the control groups, the rats were treated with saline (0.5 ml i. v.). The animals were monitored continuously for 2 h. Body temperature was maintained at 36.5 -37.5°C using a heating lamp throughout the experiment. All the studies were performed between 8.00 and 12.00.In a parallel study rats (n = 5 to 10) were treated as described above, and plasma histamine concentrations were measured spectrofluorometrically. Blood was collected from the right carotid artery before histamine injection and 2 and 4 min afterwards. Plasma was prepared as described previously [7]. Results and discussionThere were no differences in initial (before pre-treatment) MAP, pulse pressure (PP) and HR between the groups, the values being 86.63 ± 4.61 mmHg, 35.67 ± 7.08 mmHg and 346 ± 12 beats/min, respectively. In the saline pre-treated group, bolus injection of histamine transiently decreased MAP and PP by 47.25 % and 59.23 %, respectively, with no influence on HR.Pre-treatment with AM and CIT (given 15 min or 1 h before histamine) reduced histamine-induced influence on MAP and PP, and this effect was greater in AMI-than in CITtreated group (Table 1). There were no differences between Table 1. Basal (before treatment) and minimal mean arterial pressure (MAP) and pulse pressure (PP) values after histamine (10 mg/kg i. v.) injection and pre-treatment with amitriptyline (AMI; 2.7 mg/kg) and citalopram (CIT; 1 mg/kg) in rats. Results are mean ± SD; six animals per group; * p < 0.05 vs. saline-pre-treated histamine-injec...