Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle

Balwierczak, Joseph L.; Sharif, Robin; Krulan, Christine M.; Field, F P; Weiss, George B.; Miller, Mark J.S.

doi:10.1016/0014-2999(91)90416-n

Cited by 39 publications

(24 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the rabbit aorta, mesenteric and coeliac arteries show A 2 -receptor mediated vasodilatation, but in those preparations CGS21680 has a relaxing potency which is similar to that exhibited by NECA, so the A 2A subtype has been the one implicated in the vasodilatation (Balwierczak et al, 1991). However, in vascular tissues such as the dog coronary artery and saphenous vein, guinea-pig aorta (Balwierczak et al, 1991), rat mesenteric bed (Rubino et al, 1995;Prentice et al, 1997) as well as in the rat duodenum and urinary bladder (Nicholls et al, 1992) CGS21680 is very weak whereas NECA is a potent agonist, thus suggesting the presence of the A 2B subtype in those tissues. In the pig intravesical ureter, the low potency showed by CGS21680, as well as the lack of blocking e ect produced by ZM 241385, a selective antagonist of A 2A adenosine receptors, on relaxations to adenosine or NECA (Poucher et al, 1995), suggest that the adenosine-induced relaxation is mediated through activation of the A 2B -subtype.…”

Section: Discussionmentioning

confidence: 98%

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

Hernández¹,

Barahona²,

Bustamante

et al. 1999

British J Pharmacology

View full text Add to dashboard Cite

1 The present study was designed to characterize the adenosine receptors involved in the relaxation of the pig intravesical ureter, and to investigate the action of adenosine on the non adrenergic non cholinergic (NANC) excitatory ureteral neurotransmission. 2 In U46619 (10 77 M)-contracted strips treated with the adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI, 10 76 M), adenosine and related analogues induced relaxations with the following potency order:

show abstract

Section: Discussionmentioning

confidence: 98%

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

Hernández¹,

Barahona²,

Bustamante

et al. 1999

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…In both the duodenum and the bladder it was much less potent than NECA, whereas it binds to rat brain A2 receptors with an affinity roughly equal to NECA (Jarvis et al, 1989), and is roughly equipotent with NECA in relaxing a number of blood vessels (Balwierczak et al, 1991). A2 receptors have been subdivided into A2a, which have a high affinity and are found in the striatum, and A2b which have low affinity and are found elsewhere in the brain and in fibroblasts (Bruns et al, 1986;Lupica et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder

Nicholls

Hourani

Kitchen

1992

British J Pharmacology

View full text Add to dashboard Cite

1 The P1-purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclopentyladenosine (CPA) and 2-p-((carboxyethyl)phenethylamino) -5'-carboxamidoadenosine (CGS 21680), as well as the Al-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5'-triphosphate (ATP), adenylyl 5'-(fi,y-methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P1 receptors in addition to its P2-purinoceptor activity. 2 In the rat duodenum, the order of potency of the adenosine agonists was NECA > CPA > AMPPCP = adenosine > CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 nm whereas equivalent antagonism of NECA and adenosine required a concentration of 1 ym. This suggests the presence of a mixture of A1 and A2 receptors in this tissue, with CPA and AMPPCP acting on the A1 and NECA and adenosine acting on the A2 receptors. 3 In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol-induced contractions was NECA > adenosine > CPA = CGS 21680, and a concentration of DPCPX of 1 $M was required to antagonize responses to NECA and adenosine. This suggests the presence of A2 receptors in this tissue. ATP and AMPPCP each caused contractions which were not enhanced by DPCPX (1 M) which suggests that in this tissue AMPPCP was acting only via P2 receptors and had no P1 agonist activity. That AMPPCP was active on the A1 receptors in the duodenum but inactive on the A2 receptors in the bladder implies that it has selectivity for the A1 subtype.4 That CGS 21680, which has been reported to bind selectively to the high affinity A2a subclass of A2 receptors, had a very low potency on the A2 receptors in the duodenum and in the bladder suggests that these receptors are of the low affinity A2b subclass.

show abstract

“…its potential role in vascular tone (25,26), we determined BP in the A 2B AR-KO mice under basal conditions and in response to intravenous administration of adenosine at different concentrations. A 2B AR deficiency did not impact BP under basal conditions or after adenosine-induced vasodilation (Supplemental Figure 5 and Supplemental Table 3).…”

Section: Figurementioning

confidence: 99%

“…Despite this limitation, the A 2B AR has been implicated in several important biological events, including mediating vasodilation (25,26), inhibiting growth of rat aortic smooth muscle cells (27,28), and increasing the production of cytokines, such as IL-6, by vascular cells (29,30). In vitro studies described the A 2B AR as mediating augmentation of cytokine production by vascular cells (29,30), and adenosine has been described as a regulator of inflammatory response (31).…”

Section: Introductionmentioning

confidence: 99%

The A2B adenosine receptor protects against inflammation and excessive vascular adhesion

Yang

Zhang²,

Nguyen³

et al. 2006

Journal of Clinical Investigation

320

409

View full text Add to dashboard Cite

Adenosine has been described as playing a role in the control of inflammation, but it has not been certain which of its receptors mediate this effect. Here, we generated an A 2B adenosine receptor-knockout/reporter gene-knock-in (A 2B AR-knockout/reporter gene-knock-in) mouse model and showed receptor gene expression in the vasculature and macrophages, the ablation of which causes low-grade inflammation compared with age-, sex-, and strain-matched control mice. Augmentation of proinflammatory cytokines, such as TNF-a, and a consequent downregulation of IkB-a are the underlying mechanisms for an observed upregulation of adhesion molecules in the vasculature of these A 2B AR-null mice. Intriguingly, leukocyte adhesion to the vasculature is significantly increased in the A 2B AR-knockout mice. Exposure to an endotoxin results in augmented proinflammatory cytokine levels in A 2B AR-null mice compared with control mice. Bone marrow transplantations indicated that bone marrow (and to a lesser extent vascular) A 2B ARs regulate these processes. Hence, we identify the A 2B AR as a new critical regulator of inflammation and vascular adhesion primarily via signals from hematopoietic cells to the vasculature, focusing attention on the receptor as a therapeutic target.

show abstract

Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle

Cited by 39 publications

References 20 publications

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder

The A2B adenosine receptor protects against inflammation and excessive vascular adhesion

Contact Info

Product

Resources

About

Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle

Cited by 39 publications

References 20 publications

A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

Characterization of P1‐purinoceptors on rat duodenum and urinary bladder

The A2B adenosine receptor protects against inflammation and excessive vascular adhesion

Contact Info

Product

Resources

About

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

A_2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder