Pharmacological research communications最新文献

In the present study the distribution of specific binding sites for the GABA-A receptor agonist, ³H-muscimol, was studied in the rat uterus using an autoradiographic technique. Specific binding sites were present in both myometrium and endometrium suggesting a dual role for GABA in this organ.

The present experiments, carried out on the human fresh cilliary muscle, were undertaken to define whether substance P is involved as an excitatory transmitter in the contractile response evoked by electrical stimulation. Our results show that, following cholinergic and adrenergic blockade, the resistant component of contraction was completely abolished by (D-Pro²-D--Trp^7,9)-SP, a synthetic analogue of substance P with antagonistic activity. Moreover the effects of exogenous substance P were investigated.

Amiloride is one of the major molecular probes in basic and applied investigations on the physiology of cation transport in animal cells. In these cells the drug also exerts growth inhibitory activity. Recently, we discovered that amiloride causes growth inhibition also on bacterial cells. In this paper we report that medium pH influences amiloride activity on Streptococcus faecalis. The lowering of external pH causes a drop in the susceptibility of this bacterium to amiloride up to an almost complete resistance. This finding, constitutes a novel aspect of the in vitro experimental pharmacology of this diuretic potentially useful also in clinical pharmacology and in animal cell investigations.

The effects of hypotensive drug urapidil on human platelet functions were investigated.

Urapidil failed to evidence direct aggregating properties or potentiating effects. Furthermore, drug high concentrations inhibited the platelet response to ADP, PAF, collagen, adrenaline and bovine thrombin, and influenced the platelet release reaction induced by ADP and PAF.

Data indicate that urapidil possesses negligible agonistic effects on human platelet alpha 2-adrenoceptors and interferes at high concentrations with the platelet activation, as evidenced for other anti-aggregating compounds.

Simultaneous recordings of electrical and mechanical activities at different levels of the oesophagus were performed in normal men before and after physostigmine and metoclopramide injections. Various parameters of the basal oesophageal peristalsis were significantly modified following drug treatment. In particular, physostigmine injections induced a shortening of electromechanical coupling time and a reduction of the propagation velocities of the electrical and mechanical oesophageal events. Metoclopramide shortened the electromechanical coupling time but increased the electrical and mechanical propagation velocities along the oesophagus.

¹⁴C-Carmoisine (250/gmg; 1.25 × 10⁶ dpm) was incubated under strictly anaerobic conditions with resting cell suspension from stool specimens collected from male rats and human male healthy adults.

The kinetics of azoreduction was determined as amount of naphthionic acid (NA), the stable metabolite of Carmoisine produced by the activity of the anaerobic bacteria. The analytical determinations were performed by radio-HPLC technique.

There were no significant qualitative differences in the radiochro-matographic profiles of samples obtained from human and rat flora suspensions.

The calculated reduction rates were 5.03 ± 0.18 nmoles of NA/250 /ug protein/min, and 1.72 ± 0.12 nmoles of NA/250 /ug protein/min for rat and human faecal resting cells respectively. From our results it seems that the enzymatic reaction, following zero order kinetics, is similar for the two species and only the reduction rate is different.

To define the role of PAF in the acute phase of guinea pig anaphylaxis, we have measured the pulmonary (bronchoconstrictor) and hematological (thrombocytopenia, leukopenia, hemoconcentration, plasma TxB₂ increase) responses to PAF infusion and compared these responses to the effect of antigen exposure in actively and passively sensitized guinea pigs. We have also determined the effect of the structurally unrelated PAF antagonists, CV-3988 and L-652, 731 on these responses. Intravenous administration of PAF (50–400 ng/kg) caused a dose-related bronchoconstriction, thrombocytopenia, leukopenia, hemoconcentration and increase in plasma TxB₂. These PAF-induced responses were inhibited, to a variable degree, by pretreatment with CV-3988 (3 and 10 mg/kg, i.v.) and L-652, 731 (3 mg/kg, i.v.). Intravenous administration of ovalbumin to actively or passively sensitized guinea pigs caused bronchoconstriction, thrombocytopenia, leukopenia and hemoconcentration, but there was no increase in TxB₂. Moreover, the anaphylactic bronchoconstriction, thrombocytopenia, leukopenia (actively sensitized) and hemoconcentration were not inhibited by CV-3988 (10 mg/kg, i.v.) and L-652, 731 (3 mg/kg, i.v.). The different profile of changes produced by PAF and allergic anaphylaxis and the failure to alter the responses to allergic anaphylaxis with PAF antagonists suggest that PAF is not an important mediator of the acute phase of guinea pig anaphylaxis.