Adenosine receptor-mediated effects on adenylate cyclase activity in rat luteal tissue: a putative local regulatory role of adenosine in the corpus luteum.

The influence of adenosine analogs on adenylate cyclase activity was investigated in membrane preparations of luteinizedovariesand in cellhomogenates of isolatedlutealcells.The adenosine receptor agonist 5’-(Nethyl)-carboxamido adenosine (NECA) dose-dependently stimulated adenylate cyclase activityin membrane preparations of 5-day-old luteinizedovarieswith an apparent EC50 of 0.58 pM. The other adenosine analogs testedwere lesspotent in stimulating the adenylate cyclase activity with the following rank order of potency: NECA N6 -(R -phenyl-isopropyl)-adenosine< 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, NECA 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.