Inhibition of forskolin-stimulated cAMP formation by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) in rat hippocampal slices was partially obliterated by the adenosine-depleting enzyme, adenosine deaminase, or by the adenosine receptor agonist, 5'-(N-ethylcarboxamido)-adenosine, suggesting that activation of metabotropic glutamate receptors (mGluRs) modulates the release of endogenous adenosine. Consistent with this hypothesis, forskolin stimulated the release of purines from rat hippocampal slices, and this effect was reduced by 1S,3R-ACPD. To establish which transduction pathway is involved in the modulation of forskolin-stimulated purine release, we have tested the novel mGluR2 agonist, (2S,1'R,2'R,3'(R))-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), which reduced forskolin-stimulated cAMP formation but, as opposed to 1S,3R-ACPD, did not stimulate polyphosphoinositide hydrolysis. DCG-IV was highly potent and more efficacious than 1S,3R-ACPD in inhibiting forskolin-stimulated purine release. Neither DCG-IV nor 1S,3R-ACPD reduced the release of purines stimulated by depolarizing concentrations of K+, suggesting that their effect was stimulus-specific. These results indicate that, in rat hippocampal slices, activation of mGluR2 receptors attenuates the release of purines induced by forskolin, a process that amplifies the final effect of forskolin on cAMP formation asa result of A2 purinergic receptor activation. Thus, the final effect of mGluR agonists on forskolin-stimulated cAMP formation in hippocampal slices depends on both a direct inhibition of adenylyl cyclase and the inhibition of adenosine release.

INTERACTION BETWEEN METABOTROPIC RECEPTORS AND PURINERGIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES / G., Casabona; M. R., L'Episcopo; P. D., Iorio; R., Ciccarelli; E. D., Bernardis; H., Shinozaki; Nicoletti, Ferdinando; F., Caciagli. - In: BRAIN RESEARCH. - ISSN 0006-8993. - 645:1-2(1994), pp. 13-18. [10.1016/0006-8993(94)91632-2]

INTERACTION BETWEEN METABOTROPIC RECEPTORS AND PURINERGIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES

NICOLETTI, Ferdinando;
1994

Abstract

Inhibition of forskolin-stimulated cAMP formation by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) in rat hippocampal slices was partially obliterated by the adenosine-depleting enzyme, adenosine deaminase, or by the adenosine receptor agonist, 5'-(N-ethylcarboxamido)-adenosine, suggesting that activation of metabotropic glutamate receptors (mGluRs) modulates the release of endogenous adenosine. Consistent with this hypothesis, forskolin stimulated the release of purines from rat hippocampal slices, and this effect was reduced by 1S,3R-ACPD. To establish which transduction pathway is involved in the modulation of forskolin-stimulated purine release, we have tested the novel mGluR2 agonist, (2S,1'R,2'R,3'(R))-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), which reduced forskolin-stimulated cAMP formation but, as opposed to 1S,3R-ACPD, did not stimulate polyphosphoinositide hydrolysis. DCG-IV was highly potent and more efficacious than 1S,3R-ACPD in inhibiting forskolin-stimulated purine release. Neither DCG-IV nor 1S,3R-ACPD reduced the release of purines stimulated by depolarizing concentrations of K+, suggesting that their effect was stimulus-specific. These results indicate that, in rat hippocampal slices, activation of mGluR2 receptors attenuates the release of purines induced by forskolin, a process that amplifies the final effect of forskolin on cAMP formation asa result of A2 purinergic receptor activation. Thus, the final effect of mGluR agonists on forskolin-stimulated cAMP formation in hippocampal slices depends on both a direct inhibition of adenylyl cyclase and the inhibition of adenosine release.
1994
adenosine; adenosine-5'-(n-ethylcarboxamide); analogs /&/ derivatives/pharmacology; animals; camp; cycloleucine; cyclopropanes; forskolin; glycine; hippocampal slice; hippocampus; male; metabolism; metabotropic glutamate; metabotropic glutamate receptor; neurotoxins; pharmacology; physiology; purine release; purines; rats; receptors; sprague-dawley; synaptic transmission
01 Pubblicazione su rivista::01a Articolo in rivista
INTERACTION BETWEEN METABOTROPIC RECEPTORS AND PURINERGIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES / G., Casabona; M. R., L'Episcopo; P. D., Iorio; R., Ciccarelli; E. D., Bernardis; H., Shinozaki; Nicoletti, Ferdinando; F., Caciagli. - In: BRAIN RESEARCH. - ISSN 0006-8993. - 645:1-2(1994), pp. 13-18. [10.1016/0006-8993(94)91632-2]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/465954
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 10
social impact