摘要:

Abstract:The density of β‐ adrenoceptors has been determined on membranes prepared from rat myocardium. Long‐term administration of prenalterol resulted in an increase in the density of receptors, without any change in affinity. The average heart rate increase induced by intravenous prenalterol administration to denervated rats was, however, similar in the prenalterol pretreated and the control groups. We conclude that long‐term treatment with a partial β1‐adrenoceptor agonist lead to an increased β‐adrenoceptor density in th

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00598.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:An animal experiment was performed to evaluate the absorption and distribution of aluminium in serum and tissues of normal rats. The animals were intraperitoneally injected with an aluminium lactate solution at a pH adjusted to 7.0. Before starting, a short preliminary study was carried out in order to verify the validity of the treatment with aluminium lactate instead of aluminium chloride at endogenous pH 3.4. Thirty‐one rats were used in the main experiment, divided in four groups. In treated animals, the total A1‐administered dose was 75.6 mg during 78 days of treatment. Furthermore, to evaluate the influence of the parathyroid hormone on A1 absorption and/or distribution, 200 USP/rat of parathyroid hormone extract (PTH) were also administered during the last 5 days of the experiment. Aluminium content in serum, tibia, rib, brain, liver, muscle, kidney and spleen was determined. Calcium analysis in serum and bone was also performed. The highest concentrations of aluminium were found in liver and spleen, whereas the lowest level was found in the brain. The PTH effect on A1 absorption was evident in brain and b

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00599.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:This study examines the effects of diazoxide and hydralazine on gastrointestinal and vascular smooth muscle. The effect of the drugs administered individually and in combination was determined on small intestinal transit and blood pressure in adult male Sprague‐Dawley rats. Both diazoxide and hydralazine produced dose‐dependent decreases in the ratio of intestinal transit to total length. Additionally, combinations of various doses of hydralazine and diazoxide produced a greater than simple summation of the inhibitory effects on intestinal transit. The combination of diazoxide and hydralazine produced only a simple additive effect on mean arterial press

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00600.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The density (Bmax) and apparent dissociation constant (KD) of dopamine D1and D2receptors in striatum was estimated in rats of different ages (from 3.5 to 25 months) using3H‐SCH 23390 and3H‐spiperone as ligands. The density of D1and D2receptors decreases with age attaining 70 and 69% of the 3.5 months' value, respectively, whereas the KD's remain constant. The decreases in density of D1and D2receptors are parallel. Thus, throughout life the ratio between the density of D1and D2receptors remains const

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00601.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:An isolated vagus nerve‐trachea tube preparation from guinea‐pig was used to study the effect kinetics of bronchodilating β‐adrenoceptor agonists. The test compounds were added either into the fluid‐filled lumen or into the external medium and they all inhibited, dose‐dependently and completely, the vagally induced contractions. The hydrophilic compounds isoprenaline, salbutamol and terbutaline were much less potent when administered intratracheally as compared with extratracheal administration indicating a slow transport through the epithelial layer. For the lipophilic compound, D2489 (the resorcinol derivative of salmeterol), this difference was less pronounced. When terbutaline was administered as its lipophilic diisobutyrate ester prodrug, ibuterol, the difference between the routes of administration was largely eliminated. The inhibitory effect of terbutaline, but not D2489, was readily reversed by washing. Measurements of terbutaline and D2489 in the tracheal tissue and in the external medium after the intratracheal administration of the compounds support the view that a hydrophilic compound slowly passes the epithelium and is not retained in the tissue, whereas a lipophilic compound rapidly passes the epithelium and is retained by the tissue. The isolated vagus nerve‐trachea tube preparation of the guinea‐pig is well suited for the concommitant study of pharmacodynamic and pharmacokinetic properties of bronch

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00602.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effects of histamine were characterized and compared in the vascular smooth muscle of two human isolated blood vessels, the human internal mammary artery (HIMA) and the human saphenous vein (HSV). Segments of these vessels were obtained during aortocoronary bypass surgery and their intimal surface was rubbed in order to eliminate any possible influence of the endothelium. Histamine contracted both types of vessels in a concentration‐dependent manner and this effect was antagonized by the H1receptor antagonists mepyramine and cicletanine. In the case of HIMA only this antagonism was found to be competitive (pA2values of 9.3 and 7.7 for mepyramine and cicletanine, respectively). Histamine‐induced contractions were not significantly affected by phentolamine (0.3 μM). In HSV, but not HIMA, indomethacin (5 μM) significantly depressed histamine‐induced contractions (by about 30%). In the presence of the H2receptor antagonist cimetidine (10 μM), concentration‐response curves of histamine‐induced contractions were significantly shifted to the left in both HIMA and HSV, suggesting the presence of H2receptors mediating relaxation. HIMA and HSV precontracted by noradrenaline could be partially and concentrationdependently relaxed by histamine, only in the presence of a H1receptor antagonist. This relaxation was inhibited by cimetidine. The results show that in de‐endothelialized HIMA and HSV histamine induced mainly contraction which is sensitive to the H1receptor antagonists. Only in HIMA, nevertheless, was competitive antagonism established. In addition, histamine‐induced relaxation, antagonized by cimetidine, could be demonstrated in both precontracted vessels, indicating the presenc

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00603.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The interaction between (+)‐amphetamine and dopamine (DA) D1and D2receptors was investigated. In naïve mice, i.e., mice with intact stores of DA, both the selective D1antagonist SCH23390 and the selective D2antagonist spiperone blocked the locomotor stimulation produced by (+)‐amphetamine. The selective D1agonist SKF38393 (6 mg/kg intraperitoneally) did not produce a consistent dose‐dependent effect on the response to (+)‐amphetamine in naïve mice. In mice depleted of DA with reserpine 24 hr before a challenge with (+)‐amphetamine, neither SCH23390 nor spiperone were completely effective in blocking (+)‐amphetamine. A combination of spiperone plus SCH23390 was, however, more effective than either drug alone, although significant activity remained even after the combination. In mice pretreated with reserpine and various doses of α methyl‐p‐tyrosine (αMPT, intraperitoneally), the degree of stimulation produced by (+)‐amphetamine was dependent on the amount and frequency of αMPT dosage – the higher and more frequent the dose, the more effective the blockade. In these animals, both SKF38393 and the selective D2agonist quinpirole potentiated the stimulation induced by (+)‐amphetamine when the dose of αMPT was not maximal. However, in those animals pretreated with reserpine plus two doses each of 400 mg/kg αMPT, neither SKF38393 nor quinpirole were effective in potentiating (+)‐amphetamine. Nevertheless, when SKF38393 and quinpirole were administered simultaneously to these mice, marked locomotor stimulation occurred implying that the pretreatment itself had not rendered the mice incapable of locomotion. The data indicate that (+)‐amphetamine produces excitation in naïve mice by an indirect action on D1and D2receptors, both of which must be stimulated for activation to occur. In animals depleted of DA with less than optimal doses of αMPT, (+)‐amphetamine could still release enough DA to stimulate D1and D2receptors, as either SKF38393 or quinpirole could potentiate the excitation induced by (+)‐amphetamine. However, in mice pretreated with the highest doses of αMPT, (+)‐amphetamine was virtually inactive even when combined with either a D1or a D2agonist, implying a lack of relea

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00604.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Xenopus embryos, treated for three days from the early cleavage stage with the calcium channel blocking drugs nifedipine, diltiazem, verapamil or nicardipine continue to develop in water. By the seventh day many developmental abnormalities appear, the most reproducible affecting the central nervous system, failure of forebrain development, synophthalmia and neural tube defect. Other anomalies include failure of mandibular growth and malrotation of the gut. Failure of water and electrolyte transport are indicated by severe oedema in some animals. The defects appear to relate to calcium ion antagonism, and provide a pharmacological model for some forms of teratogenesis in which large populations can be studied readily.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00605.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effects of three different concentrations (about 10, 100 and 1000 μM) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis,14C‐valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near‐constant specific radioactivity of precursor. Toluene concentrations were measured by head‐space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20–30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis ad

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00606.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Göttingen mini‐pigs were given atropine and anaesthetized with one of the following drug combinations: 1) azaperone+metomidate, 2) acepromazine+thiopentone for endotracheal intubation, followed by halothane+methoxyflurane in oxygen. Respiration rate, arterial O2and CO2tensions, arterial pH, mean arterial blood pressure and heart rate were recorded at 15 min. intervals from 30 to 120 min. after the induction of anaesthesia. The azaperone‐metomidate combination, which requires continuous intravenous access, caused a mild respiratory acidosis, but acid‐base status was stable, whereas blood pressure and heart rate rose steadily throughout the observation period. The second combination depressed respiratory and cardiovascular function, but the condition of the animals did not deteriorate further during 2 hrs of surgical anaesthesia. Endotracheal intubation for inhalation anaesthesia should, however, be performed after a single injection of metomidate, as thiopentone tended to cause respiratory

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00607.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY