摘要:

The present study was conducted to investigate the effects of repeated administration of opiates on the binding characteristics of D1 and D2 dopamine receptors in specific rat brain regions. Male Sprague-Dawley rats (150–175 g) were adapted for 1 week under controlled conditions (22 ± 1°C,40% relative humidity, 12 h light: 12 h dark illumination cycle). After the adaptation period, rats were randomly assigned into six groups (n = 15/group) for two sets of experiments; one for D[ and the other for D2 receptor binding evaluation. In each set, group 1 served as saline control, group 2 was treated with morphine (1 mg/kg/day for 7 days) and group 3 was treated with naloxone (2 mg/kg/day for 7 days). Following the third day of morphine injection, rats showed restlessness, hyperactivity, increased urination, diarrhea, lacrimation, irritability and squealing on touch, head and body shakes and salivation just prior to morphine dosage. These observed signs are typical for morphine withdrawal. One hour after the last injection, rats were sacrificed by decapitation, brains were removed and kept at –70 °C. The frozen brains were further dissected into cortex (CTX), hypothalamus (HYPO), hippocampus (HIPP) and midbrain (MID), pooled (5/pool), homogenized and used for radioreceptor assays. For D1 binding study, 3H-SCH-23390 was used as ligand and for D2 receptor binding 3H-YM-09151-2 was employed. Following repeated morphine or naloxone treatment, Bmax values for 3H-SCH-23390 binding to membranes of HYPO and MID were increased and decreased, respectively, whereas Kdvalues were significantly decreased in both HYPO and MID of morphine and naloxone-treated animals. In rat brain CTX, both morphine and naloxone decreased Kd and Bmax values of 3H-SCH-23390 binding, however the decrease in Bmax values noted after morphine administration was not statistically significant. Decrease in both Bmax and Kd values of dopamine D! receptors were observed after naloxone but not morphine treatment in HIPP. Morphine administration increased the density of D2 receptors in HIPP and MID and decreased the affinity of 3H-YM-09151-2 binding in CTX, HIPP and MID. Naloxone treatment resulted in increased number of 3H-YM-09151-2 binding sites in CTX, HYPO and HIPP. While naloxone treatment increased Kα values of 3H-YM-09151-2 in HYPO and HIPP, it decreased these values in CTX and MID. It is concluded that repeated intermittent treatment with opiates induces alterations in D1 and D2 dopamine receptors binding properties and that these changes are regionally specific. Our findings may in part explain some pharmacological and behavioral effects of repeated administration of opiates and shed some light on the neurochemical alterations associated with opiate withdrawal since the changes in dopaminergic receptor binding observed with morphine treatment were accompanied by typical morphine withdrawal

ISSN:0031-7012    

DOI:10.1159/000139319

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Structural changes introduced into the benzothiazepine molecule have led to a compound, MR-14134 (3-[(3-dimethylamino)propyl]-2,3,4,5-tetrahydro-2[4-methoxyphenyl]-l,5-benzothiazepin-4-one oxalate). We have compared the effects of MR-14134 and diltiazem on blood pressure and heart rate in anaesthetized and pithed rats following intravenous administration as well as in anaesthetized rats after intracerebroventricular administration and on the binding of [3H]clonidine in the rat cerebral cortex. MR-14134 (0.1–5.0 mg/kg, i.v.) produced a dose-dependent hypotensive and bradycardic effect similar in intensity but lasting longer than that of diltiazem. These effects were antagonized by previous administration of yohimbine but not by atropine, propranolol or ICI 118,551. Doses of 1 mg/kg i.v. of MR-14134 did not modify either blood pressure or heart rate in pithed rats and did not affect the hypertensive response elicited by electrical sympathetic stimulation or by exogenous administration of norepinephrine in pithed rats. Intracerebroventricular administration of MR-14134 (60 µg/kg) decreased blood pressure and heart rate in rats. This effect was antagonized by yohimbine and prazosin. [3H]Clonidine-binding experiments in the rat cortex showed that neither MR-14134 nor diltiazem have affinity for α2-adrenoceptors. These results confirmed that MR-14134 has a hypotensive and bradycardic effect in which, unlike diltiazem, the central nervous system is involved. These effects were mediated, at least partly, by α2-adrenoceptors and I1 imidazoline recep

ISSN:0031-7012    

DOI:10.1159/000139320

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 ± 43 pg/g tissue) rats was lower than that of WKY (452 ± 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 ± 33 pg/g tissue) rats were higher compared to WKY (439 ± 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 ± 33 pg/g tissue) compared to WKY rats (260 ± 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY

ISSN:0031-7012    

DOI:10.1159/000139321

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Angiotensin had a dual action on the epididymal half of rat vas deferens. It potentiated electrical stimulated contraction and exerted a direct contractile effect on the muscle. The potentiation of electrically stimulated response may be mediated by presynaptic facilitation of neurotransmitter release. Muscular contractile response to angiotensin is concentration dependent. Angiotensin II was found to be much more potent than angiotensin III, and the order of potencies was angiotensin II > angiotensin I > angiotensin III. The presence of a mixture of protease inhibitors (10 µM chymostatin, 50 µM bacitracin, 10 µM leupeptin and 10 µM pepstatin) did not alter the contractile activity of angiotensin II. In contrast, angiotensin I (10 nM)-induced contraction was significantly reduced in the presence of ACE inhibitor SQ 20881 (500 nM). The angiotensin II induced contraction was not reduced by CGP 42112, a specific AT2 receptor antagonist, but was significantly inhibited by losartan, a specific ATi receptor antagonist. Losartan shifted the dose-response curve of angiotensin II to the right with a pA2 value of 8.68. In addition, p-aminophenylalanine6 angiotensin II, which is proposed as an AT2 receptor agonist, did not induce contraction. It is concluded that the AT1 receptor predominantly mediates angiotensin-induced contraction in epididymal rat vas defer

ISSN:0031-7012    

DOI:10.1159/000139322

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Pre- and postjunctional effects of four muscarinic (m)-cholinoceptor antagonists were investigated against carbachol in isolated spontaneously beating guinea pig atria which were also exposed to brief periods of electrical field stimulation. The cholinoceptor agonist carbachol concentration-dependently inhibited the contraction rate of the atria with an EC50 value of 92.3 ± 20.6 nmol/l. The m-cholinoceptor antagonists atropine, 4-DAMP (M1 and M3-selective), AF-DX 116 (M2-selective) and pirenzepine (M1-selective) shifted the concentration-response curves of carbachol to the right without modifying the maximal responses yielding pA2 values of 8.98, 8.37, 7.44 and 6.79, respectively. Electrical field stimulation increased the contraction rate of the atria which was potentiated by atropine or 4-DAMP while AF-DX 116 or pirenzepine had no significant effect. Therefore, on the basis of the findings with 4-DAMP, it is concluded that prejunctional m-cholinoceptors on the sympathetic nerve endings in guinea pig atria are inhibitory and are of the M3 subtype

ISSN:0031-7012    

DOI:10.1159/000139323

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid residue in all esterified positions of glycerol, was previously found to improve erythrocyte deformability in vitro. In this study, the in vivo antiarrhythmic and anti-ischemic effects of trilinolein in coronary ligated rats were investigated. Male Sprague-Dawley rats were anesthetized with urethane. Trilinolein, at dosages ranging from 10–11 to 10–7 g/kg, was administered intravenously 15 min before ligation of coronary artery. Also, the effect of trilinolein on arrhythmia was studied by ligating the coronary artery for 30 min, then reperfusing myocardium for 10 min. During the 30-min ischemia, trilinolein reduced not only the number of ectopic beats but also the incidence rate and duration of ventricular tachycardia. At 10–7 g/kg, trilinolein completely suppressed all ventricular arrhythmias. Ventricular arrhythmias during 10 min reperfusion were also reduced by trilinolein at similar dosages. Furthermore, the effect of trilinolein on infarct size was evaluated by occluding the coronary artery for 4 h before the infarct zone was stained and weighed. In rats subjected to 4 h coronary ligation, pretreatment with 10–7 g/kg trilinolein at 15 min prior to the coronary ligation significantly reduced infarct size. Trilinolein may protect myocardium against ischemic injury and suppress arrhythmia during ischemia and repe

ISSN:0031-7012    

DOI:10.1159/000139324

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Eight flavonoids were tested for their antiperoxidative activities against lipid peroxidation induced in liver cell membranes either by nonenzymic way (ascorbic acid-Fe2+ apigenin. These flavonoids were also tested for their influence on glutathione-related enzymes, which constitute one of the aim physiological antioxidant systems. It is concluded that the antiperoxidative effect shown by most of the flavonoids is exerted without modifying these

ISSN:0031-7012    

DOI:10.1159/000139325

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Chronic administration of a low dose of the histamine H1 receptor antagonist terfenadine (2 mg/kg/day) induced an increase in γ-glutamyltransferase serum activity in rats, 360 h after partial hepatectomy while the enzymatic activity appeared not to be affected during liver regeneration following treatment with the histamine H2 receptor antagonist cimetidine (20 mg/kg/day)

ISSN:0031-7012    

DOI:10.1159/000139326

出版商:S. Karger AG    

年代:1995

数据来源: Karger