General paper
Evidence that the inhibition of ATP release from sympathetic nerves by adenosine is a physiological mechanism

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Abstract

  • 1.

    1. Perfusion with the P1-purinoceptor agonist adenosine (1–500 μM) greatly reduced the stimulation-induced release of ATP and the initial contractile phase of the response of the guinea pig vas deferens to field stimulation.

  • 2.

    2. The inhibitory effects of adenosine (100 μM) were readily antagonised by the P1-purinoceptor antagonist, 8-phenyltheophylline (10 μM).

  • 3.

    3. Dipyridamole (10 μM), inhibited the stimulation-evoked release of ATP from the guinea pig vas deferens and reduced the initial component of contraction.

  • 4.

    4. These results support the view that adenosine, resulting from ectoenzymatic breakdown of ATP released as a cotransmitter from sympathetic nerve terminals, acts as a physiological prejunctional regulator of transmitter release.

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      PPADS, NF023) [48,127–131], actions of diadenosine polyphosphates on purine receptors [92,132], ectonucleotidases [133,134], and many more. Although Geoff was best known for his work on P2 receptors he also contributed extensively to research on P1 receptors (for example [88,132,135–144]). As well as short-term signalling, Geoff contributed to fields developed by others involving the roles of purinergic receptors in long-term or trophic and inflammatory signalling in vascular remodelling, restenosis and in diseases including atherosclerosis, hypertension, diabetes, thrombosis and heart conditions [25,145–147].

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      The Panx1 inhibiting drugs include probenecid, which hitherto had been considered to be a specific transport inhibitor, and also connexin mimetic peptides as off target effect [13,26]. One drug, however, that is well documented to inhibit ATP release and nucleoside flux, dipyridamole [4,27], did not affect Panx1 channels. We, therefore, tested whether the second, probenecid insensitive component of ATP release by erythrocytes was sensitive to dipyridamole.

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    Present address: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, U.K.

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