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41.
Dirk Martens Martin J. Lohse Bernhard Rauch Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(3):342-348
Summary The aim of the present study was the characterization of adenosine receptors in isolated rat ventricular myocytes. The CAMP-levels of rat ventricular myocytes in the presence of 1 mol/l isoprenaline were reduced by up to 48% by adenosine analogues; the rank order of potency was: R-N6-phenylisopropyladenosine (IC50 60 nmol/1), 5-N-ethylcarboxamidoadenosine (IC50 360 nmol/l) and S-N6-phenylisopropyladenosine (IC50 16 ol/l). The adenosine receptor antagonist XAC (xanthine amine congener) antagonized the effect of R-N6-phenylisopropyladenosine in a concentration-dependent manner with a Ki-value of 20 nmol/l. The A1 receptor-selective radioligand R-N6-125I-p-hydroxyphenylisopropyladenosine bound to membranes prepared from rat ventricular myocytes in a saturable manner with a B
max of 17.7 fmol/mg protein and a K
D-value of 1.1 nmol/l. Adenosine analogues competed for the binding with the same rank order of potency as for the inhibition of the isoprenaline-induced cAMP-increase. GTP inhibited radioligand binding with an IC50-value of 73 ol/l. These results suggest the presence of A1 adenosine receptors on rat ventricular myocytes, which mediate an inhibition of adenylate cyclase. The receptors may be responsible for the effects of adenosine and its analogues on the heart.Abbreviations
125I-HPIA
R-N6-125I-p-hydroxyphenylisopropyladenosine
- PIA
N6-phenylisopropyladenosine
- NECA
5-N-ethyl-carboxamidoadenosine
- XAC
8-4-[([(2-aminoethyl)aminocarbonyl]methyl)oxy]phenyl-1,3-dipropylxanthine (xanthine amine congener)
- Ro 20-1724
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone
- ScAMPTME
2-O-monosuccinyladenosine-3,5-cyclic monophosphate tyrosyl methyl ester
- HEPES
N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid
- GTP
guanosine-5-tri-phosphate
Send offprint requests to D. Martens 相似文献
42.
头穴透刺对急性脑梗死大鼠脑组织中cAMP、cGMP含量的影响 总被引:6,自引:0,他引:6
目的:探讨头穴透刺治疗急性脑梗死的作用机理。方法:采用放免技术,检测头穴透刺对急性脑梗死大鼠脑组织中cAMP、cGMP含量的影响。结果:头穴透刺后可使大鼠脑组织中cAMP含量明显升高,cGMP含量下降,使cAMP/cGMP比值趋于正常。结论:头穴透刺可以通过调节cAMP、cGMP含量及二的比值,改善梗死区脑组织供血,从而取得治疗效果。 相似文献
43.
目的 :研究多巴胺 1(DA1)受体激动剂非诺多泮 (fenoldopam ,FODA)对犬肾动脉cAMP含量的影响。方法 :利用放射免疫分析技术 ,测定FODA对犬肾动脉DA1受体cAMP生成量的影响。结果 :FODA可呈浓度依赖性激活肾动脉腺苷酸环化酶活性 ,增加cAMP生成量 ,选择性DA1受体阻断剂SCH2 3390能够显著减少FODA所引起的肾动脉cAMP生成量。结论 :DA1受体激动剂对肾血管的舒张反应可能与cAMP生成量的变化有着密切关系。 相似文献
44.
Sondra Barrett Norman Honbo Joel S. Karliner 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(4):384-393
Summary We studied adrenergic regulation of cellular cAMP in neonatal rat ventricular myocytes. Since CAMP content depends on synthesis, breakdown and egress, the contribution of each of these mechanisms was assessed. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, cAMP accumulation stimulated by the -adrenoceptor agonist (–)-isoprenaline was diminished when the mixed + adrenoceptor agonist (–)-noradrenaline was coincubated with (–)-isoprenaline. Moreover, adenylyl cyclase activation stimulated by (–)-isoprenaline was decreased by (–)-noradrenaline and by the selective a1-adrenoceptor agonists (–)-phenylephrine and methoxamine, suggesting that -adrenoceptor agonism regulates CAMP metabolism through its effect on the synthetic pathway. Evidence for 1-adrenoceptor mediation of this response was enhancement of (–)-noradrenaline-induced cAMP generation by the selective 1-adrenoceptor antagonist terazosin (10 nmol/l). The selective 2-adrenoceptor antagonist yohimbine (10 nmol/l) had no effect. The 1-adrenoceptor mediated depression of (–)-isoprenaline-stimulated CAMP generation and adenylyl cyclase activation was prevented by terazosin and in separate experiments markedly enhanced by pertussis toxin pretreatment, suggesting involvement of a guanine-nucleotide regulatory protein in this process.Occupation of the 1-adrenoceptor by (–)-noradrenaline did not accelerate the rate of CAMP breakdown in the absence of phosphodiesterase inhibition. Furthermore, there was no enhancement of total phosphodiesterase activity by (–)-noradrenaline in the presence of (–)-propranolol. By contrast, pertussis toxin pretreatment augmented phosphodiesterase activity. Neither pertussis toxin nor (–)-noradrenaline increased CAMP egress.We conclude that in rat neonatal cardiac myocytes agonist occupation of the 1-adrenoceptor inhibits -adrenoceptor stimulated CAMP accumulation most likely by coupling to a guanine nucleotide inhibitory protein.Supported by a grant from the Department of the Veterans Affairs Research Service and Program Project Grant HL 25847 from the National Heart, Lung and Blood Institute 相似文献
45.
目的 观察支气管哮喘不同状态时外周淋巴细胞肾上腺素能受体 (βAR)及β2 ARmRNA水平的变化。方法 用放射配基结合受体分析法 ,放射免疫法 ,逆转录聚合酶链反应 (PT PCR)及原位杂交等方法测定哮喘患者不同状态下 β2 AR密度 ,β2 ARmRNA水平 ,血浆cAMP和cGMP水平。结果 缓解期哮喘患者外周淋巴细胞 βAR的密度较正常人明显升高 ,血浆cAMP水平无显著差异 ,而发作期哮喘患者βAR及血浆cAMP水平均较正常人明显降低 ;缓解期哮喘患者外周淋巴细胞β2 ARmRNA水平与正常人无显著差异。结论 βAR数量、功能及其信使核糖核酸水平与哮喘不同发病状态有关 ,其改变仅为哮喘病程中伴随出现的变化 ,不是其发病的原发因素。 相似文献
46.
目的:观察8-Br-cAMP对人肺癌NSCLC-3细胞凋亡相关基因表达的影响.方法:将体外培育的NSCLC-3细胞分为实验组和对照组,采用原位杂交方法观察8-Br-cAMP对NSCLC-3细胞c-myc、bcl-2基因表达的影响.结果:8-Br-cAMP处理后的实验组较未加8-Br-cAMP的对照组c-myc、bcl-2基因表达降低(P<0.01).结论:8-Br-cAMP可下调与NSCLC-3细胞凋亡相关的c-myc、bcl-2基因表达. 相似文献
47.
48.
L. Rifas L. L. Dawson L. R. Halstead M. Roberts L. V. Avioli 《Calcified tissue international》1994,54(6):505-510
Human hypophosphatemic vitamin D-resistant rickets (X-linked hypophosphatemia-XLH) is characterized by hypophosphatemia, a decreased tubular reabsorption of phosphate (Pi) and defective skeleton mineralization. Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent phosphate transport in isolated osteoblasts derived from the calvaria of normophosphatemic and hypophosphatemic mice. Initial rates of phosphate uptake by normal and Hyp osteoblasts showed similar slopes. Osteoblasts from both normal and Hyp mice exhibited saturable, sodium-dependent phosphate transport with apparent Vmax and Km values not significantly different (normal mice, Vmax=24.30±3.45 nmol/mg prot. 10 min, Km=349.49±95.20 mol/liter; Hyp mice, Vmax=23.03±3.41 nmol/mg prot. 10 min, Km=453.64±106.93 mol/liter, n=24). No differences were found in the ability of normal and Hyp osteoblasts to respond to Pi transport after 5 hours of Pi deprivation. Both cell types exhibited a similar increase in cAMP in response to PTH. The accumulated results demonstrate that Pi uptake and transport in normal and Hyp mouse osteoblasts is a sodium-dependent saturable process. As osteoblast Pi uptake and transport is apparently normal in the Hyp mouse model of XLH, the osteoblastic failure described for the Hyp mouse should be attributed to other mechanism(s). 相似文献
49.
P. M. Larkman J. S. Kelly T. Takahashi 《Pflügers Archiv : European journal of physiology》1995,430(5):763-769
5-Hydroxytryptamine (5-HT) is present in nerve fibres descending from the brainstem Raphe nuclei to motoneurones and its release is thought to exert excitatory actions. 5-HT, applied from the outside, directly depolarizes spinal and cranial motoneurones in slices. This action of 5-HT is mediated, in part, by an inwardly rectifying cationic current, I
h. In cardiac cells, an equivalent current, i
f, has been shown to be directly activated by adenosine 35-cyclic monophosphate (cAMP) applied to the inside of the patch membrane. By applying the whole-cell method to thin slices of brainstem and spinal cord, we have shown that intracellularly applied cAMP and extracellularly applied dibutyryl cAMP or forskolin mimics the inward current induced by 5-HT. The selective cAMP phosphodiesterase inhibitor, Ro 20–1724, clearly prolonged the 5-HT-induced current. Maximal doses of dibutyryl cAMP or forskolin occluded the 5-HT-induced current. The broad spectrum protein kinase inhibitors 1-(5-isoquinolinesulphonyl)-2-methlypiperazine (H-7) and N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) had no effect on the currents induced by 5-HT and forskolin. From these results, we suggest that activation of 5-HT receptors on the motoneuronal membrane stimulates formation of intracellular cAMP, thereby inducing the inward current, possibly by a direct action on I
h. 相似文献
50.