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  • Title: Adenosine analogues stimulate cyclic AMP formation in rabbit cerebral microvessels via adenosine A2-receptors.
    Author: Li YO, Fredholm BB.
    Journal: Acta Physiol Scand; 1985 Jun; 124(2):253-9. PubMed ID: 2990167.
    Abstract:
    This study has examined the accumulation of cyclic AMP in microvessels from rabbit and feline cerebral cortex induced by a series of adenosine analogues to determine the type of receptor involved. The conversion of tritium labelled adenine nucleotides to [3H]cyclic AMP was determined in [3H]adenine labelled microvessels in the presence of an inhibitor of cyclic AMP hydrolysis, rolipram (30 microM). In microvessels from both cats and rabbits two adenosine analogues, N-5'-ethylcarboxamido adenosine (NECA) and L (S)-phenylisopropyladenosine (PIA), stimulated cyclic AMP accumulation. The response was larger and more reproducible in rabbits than in cats. In rabbit cerebral microvessels the order of potency as stimulator of cyclic AMP accumulation was NECA greater than 2-chloroadenosine greater than L-PIA greater than cyclohexyladenosine (CHA) greater than D-PIA. This order of potency defines the receptor involved as being of the A2 subtype. Although the maximal response to CHA appeared to be lower than that to NECA, CHA did not inhibit the response to NECA, suggesting that it is not a classical partial agonist. In the presence of the adenylate cyclase stimulating compound forskolin (I microM) NECA was more active than in its absence (close to 30-fold increase in EC50) and also produced a maximal effect six times higher. The maximal responses to PIA and CHA increased proportionally in the presence of forskolin. These results show that rabbit cerebral microvessels possess adenosine receptors of the A2 subtype capable of stimulating the formation of cyclic AMP. The functional significance of such receptors is not known, but may be related to regulation of vascular permeability.
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