Prostaglandins influence the function of many processes including contraction of smooth muscles, the reproductive system, the nervous and cardiovascular systems, and play a significant role in allergies, dysmenorrhea, headaches, and many reproductive disorders. Despite their ubiquitous nature, the mechanisms of prostaglandin action are unclear. We propose to utilize three new tools to study prostaglandin mechanism of action: (1) a subpopulation of cells from the corpus luteum which can be obtained in high yield and purity, and which has receptors for and biological responsiveness to prostaglandins E2 and F2Alpha, (2) a series of antibodies of monoclonal origin which inhibit the binding of prostaglandins E2 and/or F2Alpha to luteal cells, and (3) analogs of prostaglandins E2 and F2Alpha which can be both radiolabeled and covalently crosslinked to receptors. These tools will be used for studies of (1) mechanisms by which PGE2 stimulates and PGF2Alpha inhibits luteal cell function, (2) determination of whether PGE2 and PGF2Alpha share a common pool or possess unique classes of receptors, and (3) structure and properties of prostaglandin receptors. To achieve these goals, luteal cells will be utilized as sources of receptors and biological responsiveness for determination of agonistic, antagonistic, and binding properties of analogs and antibodies. The analogs will allow placement of a permanent radiolabel onto receptors for studies of receptor structure and function. The antibodies will allow perturbation of prostaglandin binding and biological responsiveness and will be used for structural and functional studies. Antibodies and analogs will be utilized in tandem for mechanistic studies and for ultimate receptor purification.
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