# REGULATION OF PROSTAGLANDIN BIOSYNTHESIS IN PARTURITION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1993 · $175,599

## Abstract

Lipid metabolites including prostaglandins, leukotrienes, and platelet
activating factor (PAF), as well as various monokines, are produced during
parturition. Both fetal and maternal membranes axe implicated in this
production. Understanding the metabolic pathways involved in eicosanoid
production by these tissues is important in elucidating the steps involved
in both normal and preterm initiation of parturition. This project aims to
determine the mechanism of prostaglandin control in a well defined system,
a macrophage-like cell line, and then to apply this knowledge to the more
complex case of fetal and decidual membranes. The macrophage-like cell line
is ideal as a model because the decidua exhibits several macrophage-like
characteristics. Also, the correlation of bacterial infection and preterm
labor suggests that a common mechanism may exist in the way these two cell
types respond to stiinuli. Both responses seem to be intimately tied to the
production of prostaglandins. The putative control step in the generation
of eicosanoids is the release of arachidonic acid from the sn-2 position of
membrane phospholipids by phospholipase A2. Our laboratory has succeeded in
separating several phospholipases and solubilizing and purifying a
membrane-associated phospholipase A2 from the transformed cell line P388D
1. This cell line has the usual characteristics of a macrophage, including
the production of IL-1 and the major prostaglandins including PGE2, PGF2
alpha, and PGI2. Inhibitors of eicosanoid production in vivo will be
identified and will then be evaluated for their ability to also inhibit the
phospholipase(s) found in these cells. There should be a strong correlation
between inhibition of eicosanoid production in vivo and the inhibition in
vitro of the phospholipase actually involved in arachidonic acid release.
Use of these methods should allow us to unequivocably identify the relevant
phospholipase. Chemical inhibitors such as the anti-inflammatory compound
manoalide and its analogs will be studied in this system as well as
possible natural protein inhibitors of the lipocortin type and inhibiting
monoclonal antibodies. Once the system is perfected with the P388D 1 cell
line, we will be able to analyze human amnionic and decidual membranes in
both resting and activated forms.

## Key facts

- **NIH application ID:** 2199852
- **Project number:** 5R01HD026171-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** EDWARD A DENNIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $175,599
- **Award type:** 5
- **Project period:** 1989-09-01 → 1995-01-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199852

## Citation

> US National Institutes of Health, RePORTER application 2199852, REGULATION OF PROSTAGLANDIN BIOSYNTHESIS IN PARTURITION (5R01HD026171-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199852. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*