Elsevier

Neuroscience Letters

Volume 200, Issue 2, 17 November 1995, Pages 93-96
Neuroscience Letters

Vasoactive intestinal peptide regulates extracellular adenosine levels in rat cortical cultures

https://doi.org/10.1016/0304-3940(95)12081-EGet rights and content

Abstract

Adenosine is an important inhibitory neuromodulator in the cerebral cortex, yet it remains unclear how extracellular adenosine concentrations are regulated. Recently, it has been shown that β-adrenergic receptor stimulation in rat cortical cultures causes the accumulation of extracellular adenosine derived by enzymatic hydrolysis from adenosine cyclic monophosphate (cAMP) transported into the extracellular space. In this study we show that vasoactive intestinal peptide (VIP), in addition to activating adenylyl cyclase and promoting the accumulation of intracellular cAMP in rat cortical cultures, also causes transport of cAMP and accumulation of extracellular adenosine. We further show that the extracellular accumulation of adenosine in response to VIP can be blocked by inhibition of cAMP transport, cyclic nucleotide phosphodiesterase activity, and 5′-nucleotidase, indicating that extracellular cAMP is the source of the adenosine. Cyclic AMP transport may be a general mechanism by which a variety of neuromodulators that act upon receptors coupled to adenylyl cyclase might regulate extracellular adenosine levels and thereby inhibitory tone in the cerebral cortex.

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  • Tonic adenosine A<inf>1</inf> and A<inf>2A</inf> receptor activation is required for the excitatory action of VIP on synaptic transmission in the CA1 area of the hippocampus

    2007, Neuropharmacology
    Citation Excerpt :

    By themselves, CPA (15 nM) reduced the fEPSP slope by 49.9 ± 3.7% (n = 4) and CGS21680 (10 nM) enhanced the fEPSP slope by 10.0 ± 2.0% (n = 4). The ability of A1 and A2A receptor agonists to rescue the facilitatory effect of VIP in the presence of ADA precludes the remote possibility that VIP was facilitating synaptic transmission by enhancing the release of endogenous adenosine, as it has been proposed for the VIP enhancement of cAMP production in hippocampal slices (Rosenberg and Li, 1995). ZM241385 can inhibit A1 receptor-mediated actions in the hippocampus (Lopes et al., 1999).

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P.A.R. is supported by PHS grants (NS26830 and NS31353), an Established Investigatorship from the American Heart Association, and a Mental Retardation Core Grant to Children's Hospital.

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We wish to thank Sara Vasquez for excellent technical assistance in producing and maintaining cortical cultures.

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