Effect of adenosine A1 and A2 agonists and antagonists on cAMP and Ca2+ in cultured rat mesangial cells

Abstract

Rat glomeruli have been shown to exhibit A1 and A2 adenosine (ADO) receptors. Adenosine also contracts isolated glomeruli and cultured mesangial cells (MC). We studied the effect of the relatively selective ADO agonists R-N6-(1-methyl-1-phenylethyl)adenosine (R-PIA; A1) and 5'-(N-ethylcarboxamido)-adenosine (NECA; A2) on adenosine 3',5'-cyclic monophosphate (cAMP) levels and 45Ca influx in MC. R-PIA (10(-6) M) induced a 55% decrease in cAMP content in 5 microM forskolin-pretreated MC. NECA (10(-6) M) significantly increases by 68% the cAMP levels of forskolin-stimulated MC. NECA-included increase on cAMP was absolutely blocked by the potent A2 antagonist PD115,199 and potentiated by the A1 antagonist PD116,948. Treatment with R-PIA plus the potent A2 antagonist PD115,199 increased 45Ca uptake approximately 40%, and NECA plus A1 antagonist PD116,948 induced a 25% decrease on 45Ca uptake with respect to basal 45Ca uptake. In summary, our studies show the coexistence of functional A1- and A2-like ADO receptors in glomerular MC. The A1 receptor inhibits and the A2 stimulates cAMP accumulation. In addition, the A1 ADO receptor stimulates and the A2 inhibits calcium uptake.