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This Article Full Text Full Text (PDF) All Versions of this Article: 69/3/868    most recent biolreprod.103.017962v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cometti, B. Articles by Rosselli, M. Search for Related Content PubMed PubMed Citation Articles by Cometti, B. Articles by Rosselli, M. Agricola Articles by Cometti, B. Articles by Rosselli, M.

Oviduct Cells Express the Cyclic AMP-Adenosine Pathway¹

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.

¹ This work was supported by the Swiss National Science Foundation grants 32-55738.98 and 32-64040.00 and by NIH grant 55314.

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