The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

Alteration of Human Placental Vascular Tone by Antiarrhythmic Medications In Vitro

Antiarrhythmic and Placental Vessels. Introduction : Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro.
Methods and Results : Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO₂ 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5-hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose-dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose-dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses.
Conclusions : Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant. dosedependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.     

INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC₅₀ 2 ± 10^?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.     

Rapid tolerance against focal cerebral ischemia induced by isoflurane anesthesia is attenuated by adenosine A1 receptor antagonist in rats

The brief anesthesia with isoflurane induces rapid tolerance against focal cerebral ischemia in rats and aden-osine A1 receptor antagonist, DPCPX, attenuates the beneficial effect of isoflurane preconditioning.     

药物浓度和病因对三磷酸腺苷治疗阵发性室上性心动过速的影响

本文报告23例次ATP治疗PSVT的效果,总有效率56.5％,9例次高浓度快速注射者8例转复。器质性心脏病者副作用较多,1例冠心速注高浓度ATP后,发生心室颤动和阿-斯氏综合征。这一结果提示:药物浓度和注射速度是影响疗效的主要因素,PSVT伴AVB者疗效也很低;病因和药物浓度是决定副作用的因素。因此,对于器质性心脏病者,尤其冠心病人,应避免高浓度快速静脉注射ATP。     

Post-ischemic release of nucleosides and oxypurines in isolated rat hearts. Possible involvement of ventricular fibrillation

Summary In isolated perfused rat hearts global ischemia for 2, 5, and 15 min was produced. Depending on the duration of the ischemia, postischemic reperfusion led to the release of adenosine and its catabolites, and to more or less severe ventricular tachyarrhythmias. When ventricular fibrillation occurred, a highly significant increase in the purine release was observed compared with non-fibrillating hearts. Prevention of fibrillation by antiarrhythmic drugs decreased the purine release in a highly significant way. After only 2 min of ischemia, reperfusion did not lead to ventricular fibrillation. Electrical induction of fibrillation during the reperfusion in these hearts provoked the release of very high amounts of the purine compounds. A similar effect of electrically-induced fibrillation was also obtained in hearts without a previous ischemic period. The findings suggest that ventricular fibrillation is able to induce the release of purine derivatives from the heart.     

Chronic administration of theophylline to rats induces a post-insulin binding defect in adipocyte glucose transport

Summary To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%–30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5±0.5 and 6.7±0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that ¹²⁵I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using ¹²⁵I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.