摘要:

Lithium (5 and 20 mM) was found to inhibit the dopamine‐stimulated cyclic AMP formation in homogenates from rat striatum and olfactory tubercle, leaving basal and fluoride‐stimulated activities unaffected. The inhibition of dopamine‐stimulated adenylate cyclase was non‐competitive and dose‐dependent. However, in rats treated with lithium for four weeks, no alterations were found in basal, fluoride‐ and dopamine‐stimulated adenylate cyclase activities. It is suggested that lithium interferes with hormonal stimulation of adenylate cyclase activity by an interaction with the process regulating the transfer of the receptor‐hormone stimulus to the adenylate

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01245.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Rats and mice were fed a diet containing aspirin at levels of 0, 0.3, 0.6 and 1.2% for 1 and 4 weeks. Haemorrhagic death and/or haemorrhagic anaemia occurred in rats in a dose‐dependent manner. Prothrombin and kaolin‐activated partial thromboplastin time indices were also decreased depending on the daily doses. However, no conspicuous haemorrhagic signs were found in mice given aspirin. These results suggest marked differences in haemorrhagic effects of aspirin between rats and mice. From results of supplementary experiments with two metabolites of aspirin, salicylic acid and gentisic acid, and from the fact of close relationship between hepatic concentration of salicylic acid and haemorrhagic effects of aspirin, it is inferred that salicylic acid may be a precursor for the active metabolite(s) to cause haemorrhage. The mechanism of species differences of aspirin is discus

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01246.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Effects of theophylline on contractions induced by relevant physiological agents in tubular segments of small human placental arteries were measured in an isometric myograph. Theophylline 10−7‐ 3 × 10−3M caused marked relaxation of steady contractions produced by prostaglandin F2a(PGF2a), prostaglandin E2(PGE2), vasopressin or potassium. EC50for theophylline relaxation of the PGF2a‐ contraction was 1.6 × 10−4M. Emaxwas 91.5% relaxation. Theophylline was less potent in relaxing the potassium induced contraction. Pretreatment experiments with 10−4and 10−3M theophylline showed a pronounced decrease in contractile Emax‐values for PGF2a, PGE2and vasopressin as a possible indication of non‐competitive antagonism. The results motivate further studies to elucidate possible effects of theophylline and other xanthines on the vascular resistance and blo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01247.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Tris(1,3‐dichloro‐2‐propyl)phosphate (Tris‐CP) was metabolized to products which were mutagenic forSalmonella typhimuriwnTA100 in the presence of liver microsomes from phenobarbital (PB)‐pretreated rats and NADPH. Effects of various inhibitors and inducers of cytochrome P‐450 on Tris‐CP mutagenicity were in accordance with PB‐inducible forms of this enzyme system being responsible for the formation of mutagenic product(s). A comparison was made between the toxic potential of the two halogenated flame retardants Tris‐CP and tris(2,3‐dibromopropyl)phosphate (Tris‐BP) in 5in vitrotests. Tris‐CP was much less potent than Tris‐BP with respect to bacterial (Salmonella/microsome orSalmonella/hepatocyte assay) and mammalian (V79 cells) mutagenicity, as well as DNA repair synthesis in hepatocytes. On the other hand, Tris‐CP and Tris‐BP were both equally effective in transforming Syrian hamster embryo cellsin vitro.Tris‐CP was not nephrotoxic to rats after a single dose of 500 mg/kg intraperitoneally, whereas Tris‐BP caused extensive tubular necrosis accompanied by elevated lev

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01248.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The testicular response of di‐(2‐ethylhexyl) phthalate (DEHP), as well as the kinetics of DEHP and its primary metabolite mono‐(2‐ethylhexyl) phtalate (MEHP), were studied in immature and mature rats. After 14 daily oral doses of 1.0 g DEHP/kg body weight to 25, 40 and 60‐day‐old rats, testicular damage was observed in the youngest age group only. DEHP was not found to any significant extent in the peripheral plasma after an oral dose of 1.0 g DEHP/kg body weight. High plasma levels of MEHP were found, with maximal plasma concentrations ranging from 48 to 152 μg/ml. Thein vitroplasma protein binding of MEHP was extensive, approximately 98%, in all age groups and no age‐related difference in the elimination half‐life was observed. The amount of DEHP‐derived material excreted in urine was twice as high in 25 as in 60‐day‐old rats. The mean area under the plasma concentration‐time curve of MEHP was also significantly larger in 25 than in 40 and 60‐day‐old rats. These observations suggest that the extent of absorption, and hence total exposure to MEHP and its metabolites, is higher in young than in more mature rats after oral administration of DEHP. It seems probable that this finding is relevant to the age‐related difference in t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01249.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Intracerebroventricular injections of morphine (5–20 μg) produced a dose dependent antidiuresis in the conscious hydrated rat. Naloxone pretreatment completely abolished this antidiuretic effect, but pretreatment with a specific antidiuretic vasopressin antagonist did not change the morphine antidiuresis. The vasopressin concentration in the first voided urine after antidiuresis from morphine treated rats was found to be in the same range as the vasopressin concentration in urine from saline treated rats. Injections of 20 μg morphine intracerebroventricularly in conscious hydrated rats gave a short decrease in heart rate but not in mean arterial blood pressure. This indicates, that either liberation of vasopressin nor a fall in systemic blood pressure contribute to the morphine antidiure

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01250.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effect of a new 1,4‐dihydropyridine derivative, methyl‐1,4‐dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(2‐trifluoromethylphenyl) pyridine‐5‐carboxylate, BAY K 8644, was studied on isolated thoracic aortae obtained from male Wistar‐Kyoto rats. In rat aorta BAY K 8644 had dual actions as the compound induced contractions in the concentration range 10−8‐10−5M and relaxation at higher concentrations. In low concentrations (10−8M) BAY K 8644 increased the contractile response to both noradrenaline and potassium and shifted the concentration response curves to the left while in high concentrations BAY K 8644 (10−4M) had a relaxant effect on preparations precontracted by potassium. The contractile response to BAY K 8644 was resistant to wash out in drug free medium but was totally abolished in Ca‐free medium. Re‐addition of Ca restored the contractile response in a concentration dependent manner. BAY K 8644, 10−6M, shifted the Ca‐concentration response curve in high potassium solution to the left and increased the maximal response. Phentolamine or propranolol had no effect neither on the contractile nor on the relaxant effect of BAY K 8644. The findings suggest that BAY K 8644 acts mainly by increasing the transmembrane influx of Ca in the vascular smooth muscle cells, and that this effect could be opposite to that of nifedipine. However, in high concentrations BAY K 8644 al

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01251.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The development of myoclonic activity as a toxic effect of morphine application into the intrathecal space in rats is described. This syndrome resembled the human syndrome of action myoclonus by its spontaneous onset and its augmentation by initiation of movement or by an acoustic stimulus. It was not reversed or prevented by naloxone. This effect of morphine was associated with an increase in serotonergic activity in the spinal cord and was reduced by pretreatment with parachlorophenylalanine in doses which reduced spinal 5‐HT by ∼60%. The dose which produced this syndrome was about ten times higher than the analgesic dose applied by the same route. Other commonly used opiates such as: methadone (0.5–2 mg/kg), pethidine (2‐10 mg/kg), fentanyl (2–10 μg/kg) and ketamine (2–10 mg/kg) did not produce myoclonic‐like activity, but methadone and pethidine at the highest doses caused respiratory arrest. Fentanyl appeared to be the safest of the drugs tested since a relatively high dose, administered into the intrathecal space did not cause any side effects, while morphine was least safe of the five drugs since it produced myoclonic activity in addition to the widely documented respiratory depression. We suggest that the production of the myoclonic activity is mediated by spinal seroto

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01252.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The long‐time retention of radioactivity in mice was studied by whole‐body autoradiography after administration of 1‐14C‐alkanes (C12and C16), 1‐14C‐polychlorododecanes (56 and 68% Cl w/w), U‐14C‐polychlorohexadecane (23% Cl w/w), ethyl‐14C‐phenacetin and ring‐3H‐phenacetin. All the labelled xenobiotics, except the high‐chlorinated (68% Cl) polychloroalkane and the ring‐3H‐phenacetin, gave rise to longtime (12–60 days) retention of radioactivity in the central nervous system and in the adrenal cortex; the distribution of radioactivity within the brain corresponded to the stain intensity of myelin stained sections. Administration of 1‐14C‐fatty acids (C12and C16) and 1‐14C‐acetylcoenzyme A gave a similar distribution pattern. The lipophilic radioactivity in brain and adrenal tissue was extracted and separated with thin‐layer chromatography. In the adrenal extracts, the label co‐chromatographed mainly with cholesteryl ester, and in the brain extracts with cholesterol and with more polar lipids (mainly phosphatidyl‐choline and ‐ethanola‐mine). The brain homogenate contained a non‐extracted, probably proteinaceous, residue, with comparably high radioactivity. The results show that several14C‐labelled xenobiotics which give long time retention of radioactivity in the adrenal cortex and brain, are degraded to intermediates with the possibility to become incorporated into endogenous substances. The high‐chlorinated alkane (1) and ring‐3H‐phenacetin (2) did not give such long time retention due to its persistance towards degradation (1), and lack of labelling of the degradable part of the molecule (2). It is concluded that erroneous interpretations can be drawn from distribution studies if the routes of degradation and positio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01253.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li‐containing diet for 8 weeks (plasma‐Li 0.6–0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular nitration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium‐polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti‐diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma‐Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability resp

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01254.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY