# BIOCHEMICAL BASIS OF PROSTAGLANDINS/LEUKOTRIENES IN SKIN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 1987 · $128,561

## Abstract

Recent reports indicate that products of the lipoxygenation of arachidonic
acid termed hydroxy-eicosatetraeinoic acids (HETE's) are potent mediators
of more fundamental importance than the cyclooxygenase products
(prostaglandins, thromboxanes and prostacyclins).  The biosynthesis of
these substances in the skin are presently unknown.  The present proposal
will again pioneer:  (i) to determine whether or not and how much of these
potent lipoxygenase products:  monohydroxy-ETE (5-HETE), dihydroxy-ETE
(5,12-HETE) as well as the glutathionyl derivatives termed leukotrienes
(LTC4 and LED4) are formed in normal and abnormal epidermal preparations.
We will determine whether or not they potentiate or block the actions of
the cyclooxygenase products such as PGE2 and PGF2 in the skin.  Novel
synthesis of inhibitors of the lipoxygenase pathway will be carried out and
their effects on skin will be investigated.  (ii) An exciting revelation
from our preliminary studies is that UVB-irradiation of skin does generate
local photolytic products from 7-dehydrocholesterol, a precursor of Vit D3
in the skin.  We shall isolate, purify and test the effects of each product
on the release of arachidonic acid from keratinocytes pre-labeled with
14C-arachidonic acid (AA) and directly on the hydrolysis of AA from
1-acyl-2-[1-14C] arachydonyl-syn-glycero-3-phosphocholine by phospholipase
A2 prepared from skin.  (iii) An understanding of prostaglandin action in
the skin must include knowledge of receptors for these substances in the
tissue.  We will establish a correlation between PG-receptor activity and
cAMP or cGMP accumulation in epidermal and keratinocyte preparations, then
determine the effects of PG-antagonists on known actions of PGS and cyclic
nucleotides.  Source materials for these studies will be obtained from
normal and hyperproliferating epidermal tissues from EFA-deficient,
20:3,n9-treated skin and mouse keratinocytes in culture.  Techniques of
column chromatography, TLC, GLC and HPLC will be used.  We envisage that
these studies will reveal an immense information on the nature of
endogenous modulators of phospholipid and arachidonic acid turnover in the
epidermal tissue and keratinocyte.  These informations will form the basis
for future investigations into human skin hyperproliferative disorders and
their control.

## Key facts

- **NIH application ID:** 3155861
- **Project number:** 5R01AR030679-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **SAM.gov UEI:** TX2DAGQPENZ5
- **Principal Investigator:** VINCENT A ZIBOH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $128,561
- **Award type:** 5
- **Project period:** 1983-02-01 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155861

## Citation

> US National Institutes of Health, RePORTER application 3155861, BIOCHEMICAL BASIS OF PROSTAGLANDINS/LEUKOTRIENES IN SKIN (5R01AR030679-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155861. Licensed CC0.

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