It is well known that cAMP, an important intracellular second messenger, is released from many cells upon adenylate cyclase stimulation. Cell surface bound phosphodiesterase together with ecto-5'-nucleotidase may convert the extracellular cAMP to adenosine, which may stimulate in a paracrine and/or autocrine manner cells expressing P1 receptors. In this issue of the British Journal of Pharmacology, Chiavegatti et al. demonstrate the existence of an extracellular cAMP-adenosine cascade in skeletal muscle cells which suggests a link between adrenergic stimulation of contraction, elevated cAMP formation and release and exercise hyperaemia.
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