P 2-purinergic activation of phosphoinositide turnover is potentiated by A 1-receptor stimulation in thyroid cells

Abstract

We recently discovered that in FRTL-5 cells the P 1-purinergic agonist PIA (phenylisopropyladenosine) markedly enhanced P 2-purinergic agonist-induced responses in an IAP (islet-activating protein or pertussis toxin)-sensitive manner. In this study we tested PIA and other P 1 agonists for their permissive effects on GTP (a P 2 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 P 1 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 A 1 receptor type. As for cAMP stimulation, CADO, PIA and CHA were weaker than NECA and thus in agreement with the A 2 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 A 1- and A 2-receptor subtypes are present in FRTL-5 cells and that extracellular adenosine enhances the P 2-purinergic agonist-induced responses by stimulating an A 1 receptor which is coupled to an IAP-sensitive G-protein(s).