Modification of cardiovascular response of adenosine A2 receptor agonist by adenylate cyclase in the spinal cord of rats

doi:10.1016/S0304-3940(00)01486-5

Neuroscience Letters

Volume 293, Issue 1, 20 October 2000, Pages 45-48

https://doi.org/10.1016/S0304-3940(00)01486-5 Get rights and content

Abstract

This study was performed to investigate the influence of spinal adenosine A₂ receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by adenylate cyclase or guanylate cyclase. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection (i.t.) of adenosine A₂ receptor agonist, 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 3 nmol) produced a dose dependent decrease of BP and HR. Pretreatment with adenylate cyclase inhibitor, MDL-12,330, attenuated the depressor and bradycardiac effects of CPCA (2 nmol), but not with guanylate cyclase inhibitor, LY-83,583. These results suggest that adenosine A₂ receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that the depressor and bradycardiac actions are mediated by adenylate cyclase.

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Involvement of guanylate cyclase in the cardiovascular response induced by adenosine A<inf>2B</inf> receptor stimulation in the posterior hypothalamus of the anesthetized rats
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Cardiovascular inhibitory effects induced by the posterior hypothalamic adenosine A₂ receptors were suggested by our previous reports. In this experiment, we examined the influence of the posterior hypothalamic adenosine A_2B receptors on central cardiovascular regulation of blood pressure (BP) and heart rate (HR). Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 2 nmol), an adenosine A₂ receptor agonist, showed the decrease of arterial blood pressure and heart rate, and the alloxazine, an adenosine A_2B receptor antagonist, partially blocked the depressor and bradycardiac effects of CPCA (2 nmol). To examine the role of adenosine A_2B receptors among the adenosine A₂ subtypes, we applied the 5′-N-Ethylcarboxamidoadenosine (NECA), an adenosine A_2B receptor agonist, to the posterior hypothalamus. Injection of NECA (1, 4 and 8 nmol) produced a dose-dependent decrease of arterial blood pressure and HR. Pretreatment with alloxazine (5 nmol) partially blocked the depressor and bradycardiac effects of NECA (4 nmol). Also, pretreatment with LY-83,583 (5 nmol), a soluble guanylate cyclase inhibitor, attenuated the depressor and bradycardiac effects of NECA (4 nmol). However, pretreatment with MDL-12,330 (10 nmol), an adenylate cyclase inhibitor, did not affect these effects of NECA (4 nmol). These results suggest that adenosine A_2B receptor in the posterior hypothalamus plays an inhibitory role in central cardiovascular regulation, and that guanylate cyclase mediates the depressor and bradycardiac actions of adenosine A_2B receptors.
The role of intraspinal adenosine A<inf>1</inf> receptors in sympathetic regulation
2004, European Journal of Pharmacology
Using a splanchnic nerve-spinal cord preparation in vitro, we have previously demonstrated that tonic sympathetic activity is generated from the thoracic spinal cord. Here, we sought to determine if adenosine receptors play a role in modulating this spinally generated sympathetic activity. Various adenosine analogs were applied. N⁶-Cyclopentyladenosine (CPA, adenosine A₁ receptor agonist) and 5′-N-ethylcarboxamidoadenosine (NECA, adenosine A₁/A₂ receptor agonist) reduced, while N⁶-[2-(4-aminophenyl)ethyl]adenosine (APNEA, non-selective adenosine A₃ receptor agonist) did not alter sympathetic activity. The inhibitory effect of CPA or NECA on sympathetic activity was reversed by 8-cyclopentyltheophylline (CPT, adenosine A₁ receptor antagonist) or abolished by CPT pretreatment. In the presence of 3,7-dimethyl-1-propargylxanthine (DMPX, adenosine A₂ receptor antagonist), sympathetic activity was still reduced by CPA or NECA. Sympathetic activities were not changed by applications of the more selective adenosine A₂ or A₃ receptor agonists or antagonists, including 4-[2-[[6-amino-9-(N-ethyl-β-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS21680), 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385), 2-chloro-N⁶-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Chloro-IB-MECA), and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS1191). These findings exclude a possible involvement of A₂ or A₃ receptors in sympathetic regulation at the spinal levels. Interestingly, CPT alone did not affect sympathetic activity, suggesting that adenosine A₁ receptors are endogenously quiescent under our experimental conditions. We conclude that intraspinal adenosine A₁ receptors may down-regulate sympathetic outflow and serve as a part of the scheme for neuroprotection.
Modification of cardiovascular response of posterior hypothalamic adenosine A<inf>2</inf> receptor stimulation by adenylate cylase, guanylate cyclase and by K<inf>ATP</inf> channel blockade in anesthetized rats
2003, Neuroscience Letters
Cardiovascular inhibitory effects induced by posterior hypothalamic adenosine A₂ receptors and their modulation by nitric oxide were suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine A₂ receptor stimulation by adenylate cyclase, guanylate cyclase and ATP-sensitive K⁺ channel in the posterior hypothalamus. Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of adenosine A₂ receptor agonist 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease of blood pressure and heart rate. Pretreatment with adenosine A₂ receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and bradycardiac effects of CPCA (5 nmol). Pretreatments with adenylate cyclase inhibitor MDL-12,330 (10 nmol) and guanylate cyclase inhibitor LY-83,583 (5 nmol) attenuated the depressor and bradycardiac effects of CPCA (5 nmol). In addition, pretreatment with ATP-sensitive K⁺ channel blocker glipizide (20 nmol) attenuated the depressor and bradycardiac responses of CPCA (5 nmol). These results suggest that posterior hypothalamic adenosine A₂ receptors play an inhibitory role in the central cardiovascular regulation and that both adenylate cyclase and guanylate cyclase mediate the depressor and bradycardiac actions of adenosine A₂ receptors. Also, ATP-sensitive K⁺ channel mediates the posterior hypothalamic cardiovascular regulations of adenosine A₂ receptors.
The involvement of nitric oxide on the adenosine A<inf>2</inf> receptor-induced cardiovascular inhibitory responses in the posterior hypothalamus of rats
2002, Neuroscience Letters
This study was performed to investigate the putative relationship between nitric oxide (NO) and adenosine A₂ receptors on central cardiovascular regulation in the posterior hypothalamus of rats. Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of adenosine A₂ receptor agonist 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease of blood pressure and heart rate. Pretreatment with adenosine A₂ receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and bradycardiac effects of CPCA (5 nmol). Pretreatment with soluble guanylate cyclase inhibitor LY-83,583 (5 nmol) attenuated the depressor and bradycardiac effects of CPCA (5 nmol). In addition, pretreatment with NO synthase inhibitor N^G-nitro-l-arginine methyl ester (40 nmol) attenuated the depressor and bradycardiac responses of CPCA (5 nmol). These results suggest that adenosine A₂ receptor in the posterior hypothalamus plays an inhibitory role in central cardiovascular regulation and that NO participates in the inhibitory response induced by adenosine A₂ receptor stimulation in the posterior hypothalamus.

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Modification of cardiovascular response of adenosine A2 receptor agonist by adenylate cyclase in the spinal cord of rats

Abstract

Brain Res.

Brain Res. Bull.

Brain Res.

Neuron

Neurosci. Lett.

Neurosci. Lett.

Trends Pharmacol. Sci.

Life Sci.

Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-diproxylxanthine to rat brain membranes

Naunyn-Schmiedebergs Arch. Pharmacol.

Adenosine A1 and A2 receptors of the substantia gelatinosa are located predominantly on intrinsic neurons: an autoradiographic study

J. Pharmacol. Exp. Ther.

Modification of cardiovascular response of adenosine A₂ receptor agonist by adenylate cyclase in the spinal cord of rats

Binding of the A₁-selective adenosine antagonist 8-cyclopentyl-1,3-diproxylxanthine to rat brain membranes

Adenosine A₁ and A₂ receptors of the substantia gelatinosa are located predominantly on intrinsic neurons: an autoradiographic study