Forskolin Stimulation of Cyclic AMP Accumulation in Rat Brain Cortex Slices Is Markedly Enhanced by Endogenous Adenosine

DeLapp, Neil W.; Eckols, Kris

doi:10.1111/j.1471-4159.1992.tb09301.x

Cited by 24 publications

(7 citation statements)

References 16 publications

(12 reference statements)

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“…However, in the cerebellum, we were unable to provide evidence for inhibition of forskolin-stimulated cyclic AMP generation by concentrations of CPA active in the cortex. At relatively high concentrations of CPA, a direct stimulation of [3H]-cyclic AMP generation was observed, together with an enhancement of the forskolin response, presumably through activation of A2b receptors (DeLapp & Eckols, 1992). We were also unable to observe adenosine receptor potentiation of histamine-stimulated phosphoinositide turnover in the guinea-pig cerebellum, although this phenomenon is present in cerebral cortex (Hill & Kendall, 1987) (Bruns et al, 1987b;Jarvis et al, 1989) and mouse (Wojcik & Neff, 1983).…”

Section: Discussioncontrasting

confidence: 58%

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Hernández

Kendall

Alexander

1993

British J Pharmacology

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1 The effects of adenosine receptor agonists on cyclic nucleotides accumulation were investigated in adult guinea-pig cerebellar slices by use of radioactive precursors. 2 Adenosine elicited a rapid and maintained increase in cyclic AMP, that was fully reversed upon addition of adenosine deaminase. Adenosine analogues stimulated cyclic AMP generation up to 40 fold with the rank order of potency: 5'-N-ethylcarboxamidoadenosine (0.6 tM) > 2-chloroadenosine (6p1M)>adenosine (13 iM). CGS 21680 (10pM) elicited only a small stimulation (1.2 fold).3 The cyclic AMP response to NECA was reversed by the 1,3-dipropylxanthine-based adenosine receptor antagonists 8-[4-[[[[(2-aminoethyl) (PD 115,199) with estimated apparent inhibition constants of 15, 81 and 117nM, respectively. 4 Pretreatment with adenosine also potentiated the cyclic GMP response to sodium nitroprusside, abolishing the decline in [3H]-cyclic GMP observed with sodium nitroprusside alone, and allowing [3H]-cyclic GMP levels to be maintained for at least an additional 10 min. This potentiation was fully reversed by adenosine deaminase. 5 Adenosine analogues potentiated the sodium nitroprusside-elicited cyclic GMP generation with the rank order of potency: 5'-N-ethylcarboxamidoadenosine (0.7 JIM)> 2-chloroadenosine (6 JM)> adenosine (42 JIM). 6 NECA potentiation of cyclic GMP formation was reversed by the antagonists XAC, DPCPX and PD 115,199 with apparent inhibition constants of 17, 102 and 242 nM, respectively. 7 The similar potencies of adenosine analogues and xanthine antagonists for stimulation of cyclic AMP and potentiation of cyclic GMP lead to the suggestion that these phenomena are mediated through the same adenosine receptor, the A2b receptor. Furthermore, we suggest that potentiation of the sodium nitroprusside-induced cyclic GMP response may be mediated at the level of phosphodiesterase hydrolysis of the cyclic nucleotides.

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Section: Discussioncontrasting

confidence: 58%

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Hernández

Kendall

Alexander

1993

British J Pharmacology

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“…Stimulation of cAMP formation by forskolin in brain slices is in part mediated by the endogenous adenosine acting at A2 purinergic receptors (Mante andMinneman. 1990: DeLapp andEckols, 1992). We have evidence that the inhibitory action of IS.3R-ACPD on forskolin-stimulated cAMP formation is no longer visible when adult hippocampal slices are treated with the adenosine-depleting enzyme adenosine deaminase (manuscript in preparation).…”

Section: Resultsmentioning

confidence: 94%

Developmental Changes in the Modulation of Cyclic AMP Formation by the Metabotropic Glutamate Receptor Agonist 1S,3R‐Aminocyclopentane‐1,3‐Dicarboxylic Acid in Brain Slices

Casabona

Genazzani

Stefano

et al. 1992

Journal of Neurochemistry

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Metabotropic glutamate receptors (mGluRs) have been recently described as a family of guanine nucleotide-binding regulatory protein-coupled receptors with multiple signal transduction pathways. At least one of these receptors appears to be negatively coupled to adenylyl cyclase when stably expressed in transfected cells. We have studied how activation of native mGluRs modulates cyclic AMP (cAMP) formation in brain slices prepared from rats at different ages. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,1R-ACPD), a selective agonist of mGluRs, slightly increased basal cAMP formation but reduced forskolin-stimulated cAMP formation in adult hippocampal slices, in agreement with previous results. The action of 1S,3R-ACPD on basal cAMP formation was not reproduced by the ionotropic receptor agonists N-methyl-D-aspartate, kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and was antagonised by L-2-amino-3-phosphonopropionate (L-AP-3). L-AP-3, however, did not prevent but rather mimicked the inhibitory action of 1S,3R-ACPD on forskolin-stimulated cAMP formation. In hippocampal slices from 1-, 8-, or 15-day-old rats, 1S,3R-ACPD increased basal cAMP formation but failed to reduce the action of forskolin. A similar development pattern of modulation was observed in hypothalamic slices with the difference that 1S,3R-ACPD did not stimulate basal cAMP formation in the hypothalamus of adult animals. These results suggest that inhibition of forskolin-stimulated cAMP formation by 1S,3R-ACPD is mediated by a specific mGluR subtype that is preferentially expressed in the adult.

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“…We performed studies to determine whether the 1 S,3R-ACPD-stimulated increase in basal CAMP accumulation is mediated by an increase in adenosine release or potentiation of responses to adenosine that is already present in the extracellular space. If potentiation of the CAMP response to adenosine is sufficient to account for lS,3R-ACPD-stimulated increases in basal CAMP accumulation, we would predict lS,3R-ACPD could potentiate the response to low concentrations of adenosine that do not elicit a detectable CAMP response in the absence of mGluR agonists (Delapp and Eckols, 1992). This potentiation should result in a detectable CAMP response of a magnitude similar to that normally elicited by lS,3R-ACPD.…”

Section: Thus Potentiation Of Responses To Low Levels Of Endogenousmentioning

confidence: 94%

Activation of metabotropic glutamate receptors increases cAMP accumulation in hippocampus by potentiating responses to endogenous adenosine

1993

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Metabotropic glutamate receptors (mGluRs) are coupled to effector systems through GTP-binding proteins (G-proteins) and appear to mediate slow synaptic responses in the CNS. Although mGluR-mediated increases in phosphoinositide hydrolysis have been well characterized, other mechanisms for signal transduction employed by mGluRs are poorly understood. We recently reported that the selective mGluR agonist 1-aminocyclopentane-1 S,3R-dicarboxylic acid (1S,3R-ACPD) increases cAMP accumulation in rat hippocampal slices. We have now investigated the mechanisms involved in this response. A number of G-protein-linked receptors that are not directly coupled to adenylate cyclase increase cAMP accumulation by potentiating cAMP responses to other agonists. Furthermore, previous studies suggest that glutamate increases cAMP accumulation by a mechanism that is dependent upon the presence of endogenous adenosine. Therefore, we tested the hypothesis that 1S,3R-ACPD-stimulated increases in cAMP accumulation in rat hippocampal slices are dependent upon the presence of endogenous adenosine and are mediated by an mGluR that potentiates cAMP responses to other agonists. We found that adenosine deaminase abolished 1S,3R-ACPD-stimulated cAMP accumulation whereas the adenosine uptake blocker dipyridamole enhanced this response. Additionally, adenosine receptor antagonists blocked mGluR-mediated increases in cAMP accumulation with potencies that were highly correlated with their potencies at A2 adenosine receptors. Furthermore, we performed a series of studies that suggest that 1S,3R-ACPD activates an mGluR subtype that potentiates responses to agonists of other receptors that are coupled to adenylate cyclase and that 1S,3R-ACPD-stimulated increases in cAMP accumulation in hippocampal slices are mediated by potentiation of the cAMP response to low levels of endogenous adenosine that are continuously present extracellularly.

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Forskolin Stimulation of Cyclic AMP Accumulation in Rat Brain Cortex Slices Is Markedly Enhanced by Endogenous Adenosine

Cited by 24 publications

References 16 publications

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Developmental Changes in the Modulation of Cyclic AMP Formation by the Metabotropic Glutamate Receptor Agonist 1S,3R‐Aminocyclopentane‐1,3‐Dicarboxylic Acid in Brain Slices

Activation of metabotropic glutamate receptors increases cAMP accumulation in hippocampus by potentiating responses to endogenous adenosine

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