Contraction of the rat isolated spleen mediated by adenosine A<sub>1</sub> receptor activation

Fozard, John R.; M, Milavec-Krizman

doi:10.1111/j.1476-5381.1993.tb13729.x

Cited by 26 publications

(12 citation statements)

References 19 publications

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“…The physiological basis for this phenomenon is that splenic blood volume reduces significantly during exercise, due to splanchnic blood redistribution [7, 8], and can manifest as splenic “disappearance” on nuclear imaging [9]. The degree of splenic blood volume reduction is proportional to exercise workload [7], independent of cardiac output [7], and is related to adenosine-mediated splenic vasoconstriction [10, 11]. More recently, splenic switch-off has been shown to relate to higher myocardial T2 values during dipyridamole stress, further suggesting a connection between splenic and myocardial vascular biology [12].…”

Section: Introductionmentioning

confidence: 99%

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Liu

Wijesurendra

Ariga

et al. 2016

Journal of Cardiovascular Magnetic Resonance

101

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BackgroundPerfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the “splenic switch-off” sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium.MethodsTwo-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 μg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSIspleen) and the “splenic switch-off” sign on conventional stress/rest gadolinium perfusion imaging. T1spleen values were obtained blinded to perfusion ΔSIspleen, both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects.ResultsNormal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p = 0.01, respectively). T1spleen decreased significantly during adenosine stress (mean ΔT1spleen ~ −40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔT1spleen correlated strongly with ΔSIspleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔT1spleen threshold of ≥ −30 ms during stress predicted the “splenic switch-off” sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%).ConclusionsAdenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual “splenic switch-off” sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔT1spleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0318-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Liu

Wijesurendra

Ariga

et al. 2016

Journal of Cardiovascular Magnetic Resonance

101

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“…The greatest declines were observed in the hippocampus (72%), striatum (69%), cerebellum (66%), frontal cortex (66%), parietal cortex (65%), and amygdala (64%). Outside the brain, a reduction of 11 C-MPDX uptake was observed only in the spleen, possibly reflecting specific binding of the tracer to A 1 R, because A 1 Rs are involved in splenic contraction (26). DPCPX caused a significant increase of the levels of radioactivity in rat liver and tended to increase renal activity levels as well ( Table 2), indicating that after blocking of the receptor compartment, a greater fraction of the injected dose is taken up by organs involved in tracer excretion.…”

Section: Specificity Of 11 C-mpdx Bindingmentioning

confidence: 98%

Small-Animal PET Study of Adenosine A₁ Receptors in Rat Brain: Blocking Receptors and Raising Extracellular Adenosine

Paul¹,

Khanapur²,

Rybczynska³

et al. 2011

J Nucl Med

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Activation of adenosine A 1 receptors (A 1 R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A 1 R can be visualized using 8-dicyclopropylmethyl-1-11 C-methyl-3-propyl-xanthine ( 11 C-MPDX) and PET. This study aims to test whether 11 C-MPDX can be used for quantitative studies of cerebral A 1 R in rodents. Methods: 11 C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan of the central nervous system was obtained, using a small-animal PET camera. A cannula in a femoral artery was used for blood sampling. Three groups of animals were studied: group 1, controls (saline-treated); group 2, animals pretreated with the A 1 R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 1 mg, intraperitoneally); and group 3, animals pretreated (intraperitoneally) with a 20% solution of ethanol in saline (2 mL) plus the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido [2,3-d] pyrimidine dihydrochloride (ABT-702) (1 mg). DPCPX is known to occupy cerebral A 1 R, whereas ethanol and ABT-702 increase extracellular adenosine. Results: In groups 1 and 3, the brain was clearly visualized. High uptake of 11 C-MPDX was noted in striatum, hippocampus, and cerebellum. In group 2, tracer uptake was strongly suppressed and regional differences were abolished. The treatment of group 3 resulted in an unexpected 40%-45% increase of the cerebral uptake of radioactivity as indicated by increases of PET standardized uptake value, distribution volume from Logan plot, nondisplaceable binding potential from 2-tissue-compartment model fit, and standardized uptake value from a biodistribution study performed after the PET scan. The partition coefficient of the tracer (K 1 /k 2 from the model fit) was not altered under the study conditions. Conclusion: 11 C-MPDX shows a regional distribution in rat brain consistent with binding to A 1 R. Tracer binding is blocked by the selective A 1 R antagonist DPCPX. Pretreatment of animals with ethanol and adenosine kinase inhibitor increases 11 C-MPDX uptake. This increase may reflect an increased availability of A 1 R after acute exposure to ethanol.

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“…Extracellular ATP is quickly converted to adenosine, which binds to pre-synaptic A1 adenosine receptors (Kubo and Su 1983;Wennmalm et al 1988;von Kugelgen et al 1992;Rongen et al 1996;Ralevic 2009;Macarthur et al 2011;Burnstock and Ralevic 2014). Activation of A1 adenosine receptors stimulates vascular smooth muscle contraction in the spleen (Fozard and Milavec-Krizman 1993;Tawfik et al 2005). Additional studies are required to determine interactions between CB 1 , CB 2 , A1, and P2X receptors in the splenic capsule.…”

Section: Discussionmentioning

confidence: 98%

Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1 and CB2 Cannabinoid Receptors

Simkins

Fried

Parikh

et al. 2016

J Neuroimmune Pharmacol

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The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB and CB cannabinoid receptors (Cnr1 /Cnr2 mice) were used to explore the role of endocannabinoids in spleen contraction. Spleen contraction in response to exogenous norepinephrine (NE) was found to be significantly lower in Cnr1 /Cnr2 mouse spleens, likely due to decreased expression of capsular α1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB receptor signaling. Thus, these studies demonstrate a role for CB and/or CB in noradrenergic splenic contraction.

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Contraction of the rat isolated spleen mediated by adenosine A₁ receptor activation

Cited by 26 publications

References 19 publications

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Small-Animal PET Study of Adenosine A₁ Receptors in Rat Brain: Blocking Receptors and Raising Extracellular Adenosine

Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1 and CB2 Cannabinoid Receptors

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Contraction of the rat isolated spleen mediated by adenosine A1 receptor activation

Cited by 26 publications

References 19 publications

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

Small-Animal PET Study of Adenosine A1 Receptors in Rat Brain: Blocking Receptors and Raising Extracellular Adenosine

Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1 and CB2 Cannabinoid Receptors

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Resources

About

Contraction of the rat isolated spleen mediated by adenosine A₁ receptor activation

Small-Animal PET Study of Adenosine A₁ Receptors in Rat Brain: Blocking Receptors and Raising Extracellular Adenosine