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J Damas

Publications and source records attributed to J Damas.

At least 55 records · Page 3Linked to original sources
PubMed1995

Thermolytic salivation, substance P and kinins in rats.

In the heat, rats produce a large flow of saliva that they spread on their fur. We have tested whether substance P (SP) is involved in this response by using RP 67580, a NK1 tachykinin receptor antagonist, in normal and in kininogen-deficient rats. In anaesthetized rats, the sialogogic effect of SP (1 and 5 micrograms.kg-1 iv) was inhibited by RP 67580 (50 to 2500 micrograms.kg-1 iv). SP (5 micrograms.kg-1 iv) did not modify the vascular permeability to 125I-labelled albumin in submaxillary glands but increased this permeability in periglandular soft tissues and in the ears. This effect was suppressed by RP 67580 (50 to 2500 micrograms.kg-1 ip). Unanaesthetized normal male Wistar rats were exposed to ambient temperatures of 26 degrees C (thermoneutral range) or 36 degrees C for one hour. After this time period, a loss of body weight was observed. The thermolytic water loss reached 2% of body weight. This body weight loss was reduced by atropine (3 mg.kg-1 ip) or RP 67580 (50 to 2500 micrograms.kg-1 ip). The submaxillary glands were swollen and accumulated labelled albumin. This accumulation was reduced by atropine but was not affected by RP 67580. An extravasation of labelled albumin occurred in periglandular tissues. This accumulation was not modified by atropine which induced a large oedema of the soft tissues. Protein extravasation was suppressed by RP 67580 (2500 micrograms.kg-1) which did not modify or increased the volume of the oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Pyridobenzoxazepine and pyridobenzothiazepine derivatives as potential central nervous system agents: synthesis and neurochemical study.

In order to characterize the pharmacological profile of the different chemical classes of pyridobenzazepine derivatives, a series of N-methylpiperazinopyrido[1,4]- and -[1,5]- benzoxa- and benzothiazepine derivatives were prepared. The affinities for D2, D1, 5-HT2, and cholinergic (M) receptors were measured. In comparison to dibenzazepine reference compounds, a strong decrease of the affinities was observed, less pronounced, however, for the substituted analogues. Oxazepine and thiazepine analogues like clozapine (except 8-chloro-6-(4-methylpiperazin-1-yl)-pyrido[2,3-b][1,4]benzoxazepin e (9) and 8-chloro-6-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,4]- benzothiazepine (11)) were found to be inactive against apomorphine stereotypies. In the open-field test in rats, different molecules showed a high disinhibitory activity as observed with anxiolytic drugs. Moreover, 8-chloro-5-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,5]benzoxazepine (14) presented a clozapine-like profile that was confirmed in the behavioral model in dogs and showed most of the behavioral characteristics described for antipsychotic drugs. Its neurochemical profile, in particular the 5-HT2/D2 ratio, was also compatible with atypical antipsychotic activity.

Animals↗
PubMed1994

Involvement of the kallikrein-kinin system in the salivary secretion elicited in rats by heat stress.

1. During heat exposure, rats secrete large amounts of saliva. Salivation started when body temperature exceeded 39 degrees C and was reduced by kininogen deficiency or by HOE 140, a bradykinin antagonist. This secretory response was associated with a partial depletion of glandular kallikrein from the submaxillary glands. The depletion was abolished by simultaneous treatment of the animals with an alpha- and a beta-adrenergic antagonist. During heat exposure, plasma levels of kininogens were reduced. 2. Pilocarpine and substance P induced a similar flow of saliva in normal and kininogen-deficient rats and released low amounts of kallikrein from salivary glands. Phenylephrine and isoproterenol induced a larger flow of saliva in normal rats than in kininogen-deficient rats. Both agents released large amounts of kallikrein in saliva but isoproterenol was only active at large doses. 3. During heat exposure, the blood content of submaxillary glands in normal as well as in kininogen-deficient rats increased as a function of the ambient temperature. This increase was suppressed by atropine and NG-nitro-L-arginine, a NO-synthase inhibitor, but was not modified by HOE 140. Simultaneously, a swelling of the glands and of the surrounding soft tissues occurred in normal but not in kininogen-deficient rats. Kallikrein was present in the edema fluid. 4. The kallikrein-kinin system would thus participate in heat-induced salivary secretion and kinins may be a factor responsible for electrolyte and water exchanges in the glands.

Adrenergic alpha-Antagonists↗
PubMed1993

New pyridobenzodiazepine derivatives as potential antipsychotics: synthesis and neurochemical study.

The discovery of a new, safe, atypical antipsychotic remains an important challenge. To achieve this goal, a series of N-methylpiperazinopyrido[2,3-b] [1,4]- and -[1,5]- and -pyrido[4,3-b][1,4]- and -[1,5]- benzodiazepines were synthesized. The dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities, frequently remarked in the action mechanisms of antipsychotic drugs, were determined using their respective in vitro receptor binding assays. All affinities were reduced for each compound. Optimal substituents were found to be in the 2- or 8-position for the retention of affinities, while substitution at the 5-position by acyl or alkyl groups dramatically diminished binding affinities. Pyridobenzodiazepine derivatives, such as clozapine, were found to be inactive or only weakly effective against apomorphine-mediated stereotypes in rats. In an original and complex behavioral model developed in dogs and successfully used to differentiate distinct classes of psychotropic drugs and to discriminate between typical and atypical neuroleptic drugs, 8-chloro-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b] [1,4]benzodiazepine (9), 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido [2,3-b][1,4]benzodiazepine (12), and 5-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,5]benzodiazepine (16) showed most of the behavioral characteristics previously described for neuroleptics. Their neurochemical profiles, particularly their 5-HT2/D2 pKi ratios, were compatible with an atypical antipsychotic effect. These compounds were selected for further investigation. The proposed modulations could lead to new possibilities for the pharmacochemistry of diarylazepines.

Animals↗
PubMed1993

Platelet-activating factor and the vascular effects of zymosan in rats.

Platelet-activating factor (PAF; 2.5 micrograms/kg) injected in the tail vein of anaesthetized rats increased the vascular permeability of the duodenum, paws, skin and muscles, as measured by the extravasation of 125I-labelled albumin. It did not affect the permeability of the lungs or the presence of labelled albumin in the liver and spleen. The effects of PAF were dose dependently inhibited by WEB 2086 (ID50: 1.39 to 2.09 mg/kg) and SM-12502 (ID50: 7.17 to 8.36 mg/kg). Zymosan, an activator of the alternative complement pathway (10 or 16 mg/kg), induced protein extravasation in the lungs, duodenum, paws and skin, and the accumulation of labelled albumin in the liver. The effects of zymosan on the duodenum and liver were dose dependently inhibited by WEB-2086 and SM-12502. Both PAF antagonists increased the effects of zymosan in the paws but they did not affect protein extravasation in the lungs. The hypotensive effect of PAF (0.5 micrograms/kg) was inhibited by WEB 2086 (ID50: 1.21 mg/kg) and SM-12502 (ID50: 13.4 mg/kg). Both PAF antagonists reduced the hypotensive effects of zymosan (4 or 16 mg/kg) with a similar relative inhibitory potency. PAF is the major mediator involved in the hypotensive effect of zymosan but plays only a minor role in the permeability-enhancing effect of zymosan, mostly in the splanchnic area.

Animals↗
PubMed1992

Influence of a long-acting bradykinin antagonist, Hoe 140, on some acute inflammatory reactions in the rat.

We studied the influence of Hoe 140, a bradykinin antagonist, on inflammatory reactions induced in rats. Hoe 140 reduced paw oedema induced by bradykinin alone, bradykinin plus prostaglandin (PG) E1, carrageenan, urate crystals or urate crystals plus captopril. The inhibitory effect of Hoe 140 lasted for at least 4 h. Hoe 140 also reduced plasma exudation in sponges implanted in the back of the rat. However it did not modify paw oedema induced by zymosan or by heating the paw at 55 degrees C for 30 s. Carrageenan oedema developed to a small extent in kininogen-deficient rats while the swelling induced by heating the paw of kininogen-deficient rats was the same as that measured in normal animals. Hoe 140 had no effect on the slight swelling induced by carrageenan in kininogen-deficient rats. We conclude that the kinin system is involved in inflammatory reactions induced by carrageenan, urate crystals, sponge implantation but not by zymosan and scalding.

Alprostadil↗
PubMed1992

Distribution of immunoreactive T-kininogen in rat nervous tissues.

The distribution in the nervous system of T-kininogen, the third kallikrein-resistant kininogen of the rat, was determined using bioassays and a radioimmunoassay system. In rat brain homogenates, trypsin released large amounts of a kinin-like myostimulating activity while urinary kallikrein released small amounts. The kinins released by trypsin were identified by HPLC as mostly T-kinin. Radioimmunoassays showed that a T-kininogen-like immunoreactive factor was uniformly distributed throughout the central nervous system. Higher levels were found in female rats than in male rats. Maximum levels were observed in newborn animals. A slight increase of T-kininogen content of the brain was observed after turpentine injection while T-kininogen level in liver was dramatically increased. T-kininogen plasma contamination to the nervous tissues was estimated by injecting 125I-labelled T-kininogen. The T-kininogen content of rat cultured cells and neurons was also examined. Highest levels were found in dorsal root ganglia neurons, lower levels in Schwann cells, phaeochromocytoma cells, mixed cells from spinal ganglion and in astrocytes. Immunocytochemistry showed the presence of T-kininogen in the cytoplasm of cultured dorsal root ganglia neurons and embryonic hippocampal neurons. The distribution of T-kininogen throughout the central and peripheral nervous system of the rat, the variations of its level during the life span suggest that T-kininogen would play the role of a cysteine proteinase inhibitor and not that of a T-kinin-releasing substrate in nervous tissues.

Aging↗
PubMed1992

[Regulation of arteriolar tonus and EDRF].

The physiological significance of the release of NO by endothelial cells was discussed according to the effects of inhibitors of NO formation and to the observations of Mellander et al. on the reactivity of resistance vessels in cat skeletal muscle. Whole results indicate that NO continually takes patent arteries and decreases systemic resistances. However, NO has minimal effects on the arteriolar side of the vascular tree.

Animals↗
PubMed1991

From ethnobotanical uses of Strychnos henningsii to antiinflammatories, analgesics and antispasmodics.

Strychnos henningsii Gilg is used in African traditional medicine for the treatment of various ailments, including rheumatism, gastrointestinal complaints and snake bites. Different preliminary pharmacological experiments are described. The results show that some of the reported folk medicinal applications of S. henningsii can be at least partially explained by the presence of retuline-like alkaloids, whose use could lead to new antinociceptive (antiinflammatory and analgesic) and antispasmodic drugs.

Alkaloids↗
PubMed1991

Dissociation between the effects of zymosan on the systemic and pulmonary vessels of the rat.

1. Zymosan, an activator of the alternative complement pathway, (2 to 16 mg kg-1) injected intravenously via the tail vein of anaesthetized rats, dose-dependently increased the vascular permeability of lung parenchyma, as measured by the accumulation of 125I-labelled albumin in lungs. 2. Pretreatment of the animals with cyclo-oxygenase inhibitors, indomethacin or ketoprofen (3 mg kg-1) or with the lipoxygenase and cyclo-oxygenase inhibitor, BW755C (40 mg kg-1) abolished the vascular permeability changes induced by zymosan (16 mg kg-1). Neither, the PAF antagonist, WEB 2086 (10 mg kg-1) nor the antagonist of mast cell amines, mepyramine and methysergide (3 mg kg-1) affected the plasma exudation in lungs. Zymosan did not induce any accumulation of labelled albumin in lungs of rats made leukopenic by rabbit anti-neutrophil serum. 3. Zymosan (16 mg kg-1) increased the haematocrit. This increase was not modified by indomethacin but reduced by WEB 2086. 3. Intravenous injection of zymosan (3 and 8 mg kg-1) in anaesthetized rats transiently increased right ventricular blood pressure and pulmonary arterial pressure, accelerated respiratory rate and decreased systemic blood pressure. 5. WEB 2086 largely reduced the systemic hypotension but did not affect the increase of pulmonary vascular resistance. Indomethacin inhibited the increase of blood pressure in the right ventricle and the modification of the respiratory rate. This drug did not inhibit but increased the systemic hypotension induced by zymosan. 6. Zymosan (16 mg kg-1) reduced serum complement haemolytic activity by 46%. 7. These data suggest that the pulmonary vascular changes induced by intravascular complement activation with zymosan in rats are mediated by neutrophils and prostanoids while the systemic vascular effects depend mainly on PAF.

Animals↗
PubMed1990

Proteinase inhibitors, kinins and the inflammatory reaction induced by sponge implantation in rats.

We studied the influence of aprotinin and soya bean trypsin inhibitor (SBTI) on the inflammatory reaction induced by the implantation of dry sponges in normal Wistar rats and in kininogen-deficient Brown Norway rats, during the first day after the implantation. In normal rats, aprotinin reduced the volume and total protein content of the exudates at 3 h but not thereafter. Aprotinin also markedly reduced the immunoreactive kinins and kallikrein in the exudates. Aprotinin did not modify the volume of the exudates of the Brown Norway rats. SBTI reduced the inflammatory reaction in both rat strains but did not significantly modify the formation of immunoreactive kinins. The inflammatory reaction developed more slowly in Brown Norway rats. The kinin system is thus involved during the first hours of the development of this acute inflammatory reaction. The anti-inflammatory effect of SBTI does not depend on the inhibition of kinin formation.

Animals↗
PubMed1990

Kinins and peritoneal exudates induced by carrageenin and zymosan in rats.

1. Kinins were measured by a radioimmunoassay in the inflammatory exudates induced by carrageenin or zymosan in the peritoneal cavity of normal Wistar rats and of kininogen-deficient Brown Norway rats. 2. After administration of carrageenin to normal rats, levels of immunoreactive kinins showed a single peak during the first two hours and then decreased. The presence of kinins preceded and accompanied the exudation of 125I-labelled albumin. Kinins were identified as bradykinin by chromatography. 3. Captopril, an inhibitor of kininase 2, increased the level of kinins and the volume of the exudates after carrageenin treatment. In Brown Norway rats, the volume of the exudates was small and contained little or undetectable amounts of immunoreactive kinins. 4. During zymosan-induced peritonitis, the exudates were devoid of immunoreactive kinins in both species. The volume of the exudates was larger in kininogen-deficient rats than in normal rats. 5. We conclude that in rats, the kinin system is a major factor responsible for the development of the inflammatory reactions induced by carrageenin, but is not involved in the reactions induced by zymosan.

Animals↗
PubMed1990

The significance of high molecular weight kininogen for contact activation of rat blood coagulation, in vitro.

The involvement of the high molecular weight rat kininogen in the activation of the rat contact system by kaolin-cephalin, kaolin, sulfatides and ellagic acid has been investigated, using a rat plasma congenitally devoid of this kininogen. Coagulation times induced by these activators were shorter in normal as well as in deficient rat plasma than in normal human plasma. Coagulation times were prolonged in deficient rat plasma, when the incubation times was three min or less. By kaolin or cephalin-kaolin, this prolongation disappeared when the incubation time reached ten min. The activation of plasma prekallikrein developed slowly in deficient plasma with all the triggers but reached control level after ten min of incubation. By kaolin-cephalin, the activation of Hageman factor was weak and slow in deficient plasma during the ten min of incubation. In rat, high molecular weight kininogen plays thus a role in the activation of the contact system by these triggers. But this role seems to be less important than in human plasma.

Animals↗
PubMed1989

Quantification of rat T-kininogen using immunological methods. Application to inflammatory processes.

Antibodies raised in rabbits against rat T-kininogen (alpha 1-cysteine proteinase inhibitor) were used to develop a radioimmunoassay and a nephelometric quantification for T-kininogen. These assays were specific and analytically reliable. We also described a radioimmunoassay for kinin measurement. These immunological methods have been used to study the behaviour of T-kininogen during inflammatory processes and specify the two properties of this kind of kininogen: its inhibitory capacity towards cysteine proteinases and its activity as precursor of T-kinin. Control plasma level of T-kininogen in male rats was lower than that of female rats. The maximum level was observed in plasma, liver, kidney and uterus of female rats during metestrus. After turpentine injection, T-kininogen level increased not only in plasma but also in liver and kidney. In carrageenan-induced peritoneal exudates, we found a large accumulation of T-kininogen and of immunoreactive kinins, these latter being identified by HPLC as bradykinin.

Animals↗