共查询到20条相似文献,搜索用时 15 毫秒
1.
G. Cristalli M. Grifantini S. Vittori W. Balduini F. Cattabeni 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2)
Abstract A variety of adenosine analogues have been recently evaluated in order Lo find more potent and selective agonists on adenosine receptors. The most potent adenosine analogues acting on A1 receptor, a high affinity receptor inhibitory to adenylate cyclase, are N6-substituted compounds. So 6-cyclohexyladenosine (CHA) and 6-L-phenylisopropyladenosine (L-PIA) are extremely potent agonists on A2 receptor, whereas they are relatively weak agonists on A receptor, a lower affinity receptor which is stirnulatory to cyclase, and they have no effect on the adenosine P site. 相似文献
2.
Gloria Cristalli Mario Grifantini Sauro Vittori Walter Balduini Flaminio Cattabeni 《Nucleosides, nucleotides & nucleic acids》2013,32(5):625-639
Abstract Several deaza-analogues of adenosine and 2-chloro-adenosine have been examined for their adenosine receptor affinity. It was found that the relative contribution of the nitrogen atoms of the purine moiety to binding at A1 rat brain adenosine receptor, follows the order N7 > N3 > N1. The affinity of the adenosine analogues for the adenosine rat brain receptor was besides compared with their activity as inhibitors of platelet aggregation. A synthesis of 2-chloro-1-deazaadenosine by two alternative routes starting from 7-nitroimidazo[4,5-b]pyridine-4-oxide is also reported. 相似文献
3.
《Journal of receptor and signal transduction research》2013,33(1-6):231-244
AbstractThe characteristics of adenosine receptors and adenosine uptake sites in brain are presented. High affinity adenosine receptors of the A1 type bind [3H]cyclohexyladenosine ([3H]CHA) and [3 H]diethyl-phenyl-xanthine ([3H]DPX) with 10?9 potency while adenosine uptake sites are labeled 10?10 potency with [3 H]nitrobenzyl-thioinosine ([3H]NBI). NBI does not inhibit either [3H]CHA (agonist) or [3H]DPX (antagonist) binding to adenosine receptors in brain cortical membranes and conversely CHA and other adenosine receptor ligands are very poor inhibitors of [3H]NBI binding to adenosine uptake sites. A number of other differences between the receptor and uptake site are discussed which provide rather strong evidence that these two sites are quite distinct and that the labeled ligands used represent specific probes for each site. 相似文献
4.
A. P. Ljzerman P. J. M. Van Galen Th. H. W. Van Vlijmen W. Soudijn P. Nissen I. Van Wijngaarden 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1039-1047
Abstract With the aid of molecular modelling both adenosine and adenosine A, receptor antagonists belonging to various chemical classes were compared. A model for the antagonist binding site was developed. As a consequence 1H-imidazo[4, 5-c]-quinolin-4-amines were synthesized, constituting a novel class of potent non-xanthine adenosine receptor antagonists. 相似文献
5.
Hiroyasu Nakata 《Nucleosides, nucleotides & nucleic acids》2013,32(5):983-991
Abstract A1 adenosine receptors were purified to an apparent homogeneity from rat brain and testicular membranes by a novel affinity chromatography system using xanthine amine congener (XAC) as an immobilized ligand. This affinity chromatography was also useful for the purification of human brain A1 adenosine receptor. 相似文献
6.
Michael F. Jarvis Michael Williams Un Hoi Do Matthew A. Sills 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1201-1202
Abstract The use of xanthine adenosine receptor antagonists such as 1,3-dipropyl-8-phenylxanthine (DPX) as radioligands for the characterization of adenosine receptor Pharmacology have been limited by their high lipophilicity, low specific activity, and their general lack of selectivity and affinity for adenosine receptors. Recent attempts to address the technical problems associated with this class of compounds has resulted in the development of several xanthine derivatives (e.g. the functionalized xanthine congeners [3H]XCC and [3H]XAC2, and [3H]CPX3) which bind with high and selective affinity to the adenosine A1 receptor subtype. Based on efforts to optimize non-xanthine adenosine receptor antagonists, CGS 15943, a derivative of the pyrazoloquinazoline benzodiazepine receptor inverse agonist CGS 82165, represents the first reported non-xanthine structure that potently blocks adenosine receptors6. CGS 15943 has nanomolar affinity for both A1 and A2 receptor subtypes6. However, in contrast to many of the xanthine adenosine receptor antagonists, CGS 15943 is not a phosphodiesterase inhibitor and does not interact with adenosine transporter sites6. This compound is a potent and selective adenosine receptor antagonist in vivo 7 with a solubility/affinity ratio of greater than 10007. In the present studies, the binding of [3H]CGS 15943 to the adenosine A1 receptor was characterized. 相似文献
7.
M. Milavec-krizman H. Wagner A. Kralj J. P. Evenou F. Gadient 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1127-1129
Abstract All adenosine receptor agonists, regardless of their A1/A2 selectivity ratio, dose dependently reduced blood pressure (MAP) whereas their effects on heart rate (HR) and plasma renin activity (PRA) depended on their receptor subtype selectivity. Thus an adenosine receptor agonist with an optimal A1- and A2- receptor selectivity (no increase in HR and PRA) and which does not penetrate the brain, might be a useful antihypertensive drug. 相似文献
8.
Heng T. Duong Zhan-Guo Gao Kenneth A. Jacobson 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1507-1517
Residues of the second extracellular loop are believed to be important for ligand recognition in adenosine receptors. Molecular modeling studies have suggested that one such residue, Gln 167 of the human A 3 receptor, is in proximity to the C2 moiety of some adenosine analogs when bound. Here this putative interaction was systematically explored using a neoceptor strategy, i.e., by site-directed mutagenesis and examination of the affinities of nucleosides modified to have complementary functionality. Gln 167 was mutated to Ala, Glu, and Arg, while the 2-position of several adenosine analogs was substituted with amine or carboxylic acid groups. All compounds tested lost affinity to the mutant receptors in comparison to the wild type. However, comparing affinities among the mutant receptors, several compounds bearing charge at the 2-position demonstrated preferential affinity for the mutant receptor bearing a residue of complementary charge. 13, with a positively-charged C2 moiety, displayed an 8.5-fold increase in affinity at the Q167E mutant receptor versus the Q167R mutant receptor. Preferential affinity for specific mutant receptors was also observed for 8 and 12. The data suggests that a direct contact is made between the C2 substituent of some charged ligands and the mutant receptor bearing the opposite charge at position 167. 相似文献
9.
Abstract The syntheses of three classes of adenosine analogues involving cyclosubstitution at the 6-position and functionalization at the 2-position are reported. The target molecules synthesized are stable with respect to hydrolytic deamination by mammalian adenosine deaminase, and, because of major structural changes at the 2- and 6-positions, these compounds are expected to be poor phosphorylation substrates for the kinases. Adenosine receptor binding data reveal that several of the compounds synthesized show excellent A1 receptor affinity and A2/A1 selectivity. 相似文献
10.
V. Casadó J. Mallol C. Lluis E. I. Canela R. Franco 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1141-1143
Abstract The effect of phospholipases on the membrane-bound and solubilized A1 adenosine receptor has been studied. The results indicate that phospholipids are essential for the functionality of the A1 adenosine receptor and that there is a co-solubilization of receptor and phospholipids. 相似文献
11.
Michael G Collis 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1057-1066
Abstract Adenosine receptors in isolated tissues from guinea-pigs have been investigated using agonists and antagonists. The receptor mediating decreases in rate and force of contraction of the atria is of the A1 sub-type. Responses of smooth muscle preparations to adenosine and its analogues are complex involving relaxation mediated by both A2 receptors an by non-receptor mechanisms. Contractions mediated by an A1 receptor can also be detected. 相似文献
12.
Philip J.M. van Galen Adriaan P. Ijzerman Willem Soudijn 《Nucleosides, nucleotides & nucleic acids》2013,32(2):275-291
Abstract The synthesis and A1 adenosine receptor affinity of some xanthine-7-ribosides is described. It appears that these compounds are A, receptor antagonists. The orientation of the ribose moiety, as determined by ′H-NMR spectroscopy and theoretical chemical calculations, is compared with the orientation of the ribose in the agonist adenosine. Implications for the syn vs anti modes of binding to the receptor are discussed. 相似文献
13.
Ronald J. Quinn Michael J Dooley Andre Escher Fiona A. Harden Hiranthi Jayasuriya 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1121-1124
Abstract Computer graphic analyses on a broad spectrum of adenosine receptor ligands has shown that both the A1 and A2 adenosine receptors have three binding sites. The spatial relationship of these three binding sites has been defined. Adenosine orientation at A1 and A2 is different. 相似文献
14.
G. Froldi M. De Biasi G. Fassina L. Puglisi 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1151-1153
Abstract The type of purinergic receptor involved in tracheal contraction by R-N6-phenylisopropyladenosine (PIA) and the influence of this adenosine analogue on prostaglandin release were studied in normal and in actively sensitized tracheae. Results suggest a balance between adenosine and eicosanoids in the regulation of the airway system. 相似文献
15.
Marina Cools Erik De Clercq John C. Drach 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):423-424
Abstract A paired adenosine kinase-positive/adenosine kinase-negative cell system is proposed to distinguish those adenosine analogues that need to be phosphorylated to exert their biological effects from those that are mainly targeted at S-adenosyl-L-homocysteine hydrolase. 相似文献
16.
Abstract Generalized seizures induced a widespread upregulation of adenosine A1 receptors linked to G proteins in the rat brain. Changes in receptor density were more pronounced in structures mediating seizure activity and were age-dependent. 相似文献
17.
Maarten de Zwart Regina Link Jacobien K. von Frijtag Drabbe Kunzela Gloria Cristalli Kenneth A. Jacobson Andrea Townsend-Nicholson 《Nucleosides, nucleotides & nucleic acids》2013,32(6):969-985
Abstract Various adenosine analogues were tested at the adenosine A2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A2B receptors. 5′-.N-Substituted carboxamidoadenosines were most potent. 5′-N-Ethylcarboxamidoadenosine (NECA) was most active with an ECso value of 3.1 μM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N6) of the purine ring system. The most active N6-substituted derivative N6-methyl-NECA was 5 fold less potent than NECA. C8-and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3-and 7-deazaanalogues were not active. 相似文献
18.
Background
Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation.Methods
mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart.Results
Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists.Conclusions
This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. 相似文献19.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):927-930
Abstract Synthesis of 2′-deoxy-2′-fluoro-N 6-substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A3 adenosine receptor are described. 相似文献
20.
Suhaib M. Siddiqi Xiao-duo Ji Neli Melman Mark E. Olah Rahul Jain Patricia Evans 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):693-717
Abstract The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of heterocyclic derivatives have been determined. Mono-, bi-, tricyclic and macrocyclic compounds were screened in binding assays, using either [3H]PIA or [3H]CGS 21680 in rat brain membranes or [125I]AB-MECA in CHO cells stably transfected with rat A3 receptors. Several new classes of adenosine antagonists (e. g. 5- oxoimidazopyrimidines and a pyrazoloquinazoline) were identified. Various sulfonylpiperazines, 11- hydroxytetrahydrocarbazolenine, 4H-pyrido[1,2-a]pyrimidin-one, folic acid, and cytochalasin H and J bound to A3 receptors selectively. Moreover, cytochalasin A, which bound to A1 adenosine receptors with Ki value of 1.9 μM, inhibited adenylyl cyclase in rat adipocytes, but not via reversible A1 receptor binding. 相似文献