Roanoke Times
                 Copyright (c) 1995, Landmark Communications, Inc.

DATE: TUESDAY, August 1, 1995                   TAG: 9508010088
SECTION: NATIONAL/INTERNATIONAL                    PAGE: C-4   EDITION: METRO 
SOURCE: Associated Press
DATELINE: BOSTON                                LENGTH: Medium

ASPIRIN RESEARCH MAY GO EASY ON THE STOMACH

They found how the world's most widely used drug gums up the body's machinery for making prostaglandins, the natural chemicals that are often to blame when people suffer fever, headaches or inflammation.

The research may have some practical use helping scientists design better pain and inflammation fighters that are easier on the stomach.

For decades, scientists have been closing in on the mystery of how aspirin works.

Dr. Michael Garavito and colleagues from the University of Chicago filled in the innermost intricacies of this process in a report in the August issue of the journal Nature Structural Biology.

Scientists already knew that aspirin interferes with prostaglandin H2 synthase, the enzyme the body uses to manufacture prostaglandin.

Last year, Garavito's team showed just what this enzyme looks like - a crystal with a tube running up the middle of it. Material passes through the tunnel to the core of the enzyme, where it is turned into prostaglandin.

Now, the Chicago researchers have shown what aspirin does: It blocks the tunnel.

One reason people feel lousy when they get the flu or strain their backs is that their bodies make lots of hormone-like fatty acids called prostaglandins. Part of the aspirin permanently attaches itself to a specific spot inside the tunnel, where it prevents the raw materials from getting by.

Aspirin is just one of 24 drugs used throughout the world that are known collectively as nonsteroidal anti-inflammatory drugs. They probably all work in similar ways, said Dr. Larry Marnett of Vanderbilt University.

The body actually makes two forms of the enzyme, known as PGHS-1 and PGHS-2.

PGHS-1 is found everywhere throughout the body and has a variety of uses, including protecting the stomach. PGHS-2 usually comes into play only during emergencies, such as infections or tissue damage.

As it turns out, aspirin seems to plug up the channel completely in PGHS-1. It blocks the channel only partially in PGHS-2.

``That little hint shows how maybe we could design a drug targeted to one and not the other,'' Garavito said.

In other words, it may be possible to create a pain reliever that knocks out the nasty form of PGHS while ignoring the benign variety, thus eliminating the risk of stomach ulcers.