P2-PURINERGIC ACTIVATION OF PHOSPHOINOSITIDE TURNOVER IS POTENTIATED BY A1-RECEPTOR STIMULATION IN THYROID-CELLS

We recently discovered that in FRTL-5 cells the P1-purinergic agonist PIA (phenylisopropyladenosine) markedly enhanced P2-purinergic agonist-induced responses in an IAP (islet-activating protein or pertussis toxin)-sensitive manner. In this study we tested PIA and other P1 agonists for their permissive effects on GTP (a P2 agonist)-induced inositol phosphate production and arachidonate release and found that the order of potency was PIA = CHA (cyclohexyladenosine) > NECA (N-ethylcarboxamidoadenosine) = CADO (chloradenosine). The P1 agonists also caused an inhibition of thyrotropin-induced cAMP increase in FRTL-5 cells as well as a stimulation of cAMP accumulation in IAP-treated cells. The order of potency was very similar for phosphoinositide turnover, arachidonate release and cAMP inhibition, and therefore suggestive of an adenosine A1 receptor type. As for cAMP stimulation, CADO, PIA and CHA were weaker than NECA and thus in agreement with the A2 receptor type. The order of potency of four adenosine antagonists also revealed a similarity between arachidonate release and cAMP inhibition and a difference for arachidonate release and cAMP stimulation. These results indicate that both A1- and A2-receptor subtypes are present in FRTL-5 cells and that extracellular adenosine enhances the P2-purinergic agonist-induced responses by stimulating an A1 receptor which is coupled to an IAP-sensitive G-protein(s).