Adenosine Receptor-Mediated Effects on Adenylate Cyclase Activity in Rat Luteal Tissue: A Putative Local Regulatory Role of Adenosine in the Corpus Luteum1

The influence of adenosine analogs on adenylate cyclase activity was investigated in membrane preparations of luteinized ovaries and in cell homogenates of isolated luteal cells. The adenosine receptor agonist 5'-(N-ethyl)-carboxamido adenosine (NECA) dose-dependently stimulated adenylate cyclase activity in membrane preparations of 5-day-old luteinized ovaries with an apparent EC50 of 0.58 microM. The other adenosine analogs tested were less potent in stimulating the adenylate cyclase activity with the following rank order of potency: NECA less than 2-chloro-adenosine greater than N6-(R-phenyl-isopropyl)- adenosine less than N6 -(S-phenyl-isopropyl)-adenosine. In homogenates of isolated cells from 5-day-old corpora lutea, NECA stimulated adenylate cyclase with the same EC50 as in the membranes from luteinized ovaries. The effect of NECA was antagonized by the adenosine receptor antagonist 8-phenyltheophylline. In incubated luteal cells of both 2- and 5- to 6-day-old luteinized ovaries, NEC stimulated cyclic adenosine 3', 5'-monophosphate (cAMP) accumulation and markedly potentiated luteinizing hormone-stimulated cAMP accumulation. Progesterone synthesis was also stimulated by NECA in incubated cells. The study demonstrates effects of adenosine analogs on adenylate cyclase and cAMP accumulation that fulfill the criteria for adenosine A2 receptor-mediated effects in luteal cells and membranes. These data suggest that adenosine may have a local regulatory action in luteal tissue through adenosine receptor activation.