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Female Reproductive Tract |
Center for Clinical Pharmacology,3 Departments of Medicine and Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261
Clinic for Endocrinology,4 Department of Obstetrics and Gynecology, University Hospital, Zurich, 8091 Zurich, Switzerland
The extracellular cAMP-adenosine pathway refers to the local production of adenosine mediated by cAMP egress into the extracellular space, conversion of cAMP to AMP by ectophosphodiesterase (PDE), and the metabolism of AMP to adenosine by ecto-5'-nucleotidase. The goal of this study was to assess whether the cAMP-adenosine pathway is expressed in oviduct cells. Studies were conducted in cultured bovine oviduct cells (mixed cultures of fibroblasts and epithelial cells, 1:1 ratio). Confluent monolayers of oviduct cells were exposed to cAMP (0.01–100 µmol/L) in the presence and absence of 3-isobutyl-1-methylxanthine (IBMX, 1 mmol/L, an inhibitor of both extracellular and intracellular PDE activity), 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX, 100 µmol/L, a xanthine that can inhibit extracellular or ecto-PDE activity at high concentrations), or 
,ß-methylene-adenosine-5'-diphosphate (AMPCP, 100 µmol/L, an ecto-5'-nucleotidase inhibitor) for 0–60 min. The medium was then sampled and assayed for AMP, adenosine, and inosine. Addition of exogenous cAMP to oviduct cells increased extracellular levels of AMP, adenosine, and inosine in a concentration- and time-dependent manner. This effect was attenuated by blockade of total (extracellular and intracellular) PDE activity (IBMX), ecto-PDE activity (DPSPX), or ecto-5'-nucleotidase (AMPCP). The functional relevance of the cAMP-adenosine pathway is supported by the findings that treatment with adenylyl cyclase stimulants (forskolin plus isoproterenol) resulted in the egress of cAMP (97% extracellular) into the extracellular space and its conversion into adenosine. The extracellular cAMP-adenosine pathway exists in oviduct cells and may play an important role in regulating the biology and physiology of the oviduct. This pathway also may play a critical role in regulating sperm function, fertilization, and early embryo development.
2 Correspondence: Marinella Rosselli, Department of Obstetrics and Gynecology, Clinic for Endocrinology (NORD1, D-217), University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland. FAX: 41 1 255 4439; marinella.rosselli{at}fhk.usz.ch
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