Opioids moonlighting in cell growth?

Opioids moonlighting in cell growth?

Discovered in normal nerve tissuemore than a decade ago, substances called endorphins, with their morphine-like effects, are popular subjects of both scientific research and public attention. These compounds, along with the rest of the general class of pain relievers called opioids, have been studied for their "feel-good' role. But recent reports suggest they also may help regulate both normal and malignant cell growth.

By slowing cell division, naturally occurringopioids apparently exert an inhibitory control over brain tissue development in young mice, scientists reported at last week's meeting of the Federation of American Societies for Experimental Biology in Washington, D.C.

According to Ian S. Zagon of PennsylvaniaState University's Milton S. Hershey Medical Center in Hershey, if a compound that blocks opioid receptors is injected prior to examination of the brain--thus making the body's opioids ineffective-- there is a greater-than-normal proliferation of brain cells. He told SCIENCE NEWS that an abnormal increase in cell growth is seen at times when the opioid receptors are blocked, whether the blockade is continuous during the test period or intermittent.

However, when the blockade is intermittent,the overall cell growth rate is decreased to 25 percent below normal at times when the blockade is off. Zagon attributes this to overstimulation of receptor production by the cells, in an attempt to compensate for opioid deficiency caused by the blockade. The ultimate result of the blockade by opioid-like substances results in mice that appear older than their untreated counterparts, says Zagon. For example, a nine-day-old mouse may resemble another that is two weeks old, based on appearance and behavior. But when opioid-binding in brain tissue is blocked intermittently, smaller-than-normal mice result.

These growth differences disappear by21 days after birth, an observation consistent with other studies showing that opioid receptors in certain areas of the brain disappear as the animal matures. According to Barbara H. Herman of the Brain Research Center at Children's Hospital in Washington, D.C., the level of opioids in humans drops three-fold after the first 24 hours of life.

Herman, who presented her work onopioid levels in autistic children at last fall's meeting of the Society for Neuroscience, told SCIENCE NEWS that the Pennsylvania results may help explain the link between studies suggesting abnormal opioid system development as a possible cause of autism, and her preliminary success in treating autistic children with opioid antagonists.

In other experiments, Zagon and hisco-workers have expanded their earlier studies of opioid receptors on cancer cells. They had found that opioids appear to suppress the growth of neuroblastoma, a nervous system tumor. Now they have found these receptors on cells from a wide variety of human and animal tumors, says Zagon. Although it is unclear whether this opioid system is the same as that seen in the growth-regulation experiments, the Hershey scientists say they have data suggesting that opioids can inhibit growth of these cancer cells in laboratory animals. Zagon says this inhibition is blocked by opioid antagonists.

"Maybe opioids have no function at all[in cancer] . . . but they seem to be related to growth,' says Zagon. He points out that the body's response to opioids is "extremely complex,' making it difficult to determine exactly which mechanisms might be at work in growth regulation.