Receptor-mediated regulation of neuropeptide gene expression in astrocytes.
One of the functions of glial receptors is to regulate synthesis and release of a variety of neuropeptides and growth factor peptides, which in turn act on neurons or other glia. Because of the potential importance of these interactions in injured brain, we have examined the role of two different receptors in the regulation of astrocyte neuropeptide synthesis. Stimulation of beta-adrenergic receptors on type 1 astrocytes resulted in increased mRNA and protein for the proenkephalin (PE) and somatostatin genes. This receptor also increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The potential role of opiate receptors was examined in several ways. Treatment of newborn rats for 7 days with the opiate antagonist naltrexone, prior to preparation of astrocytes, had no effect on PE mRNA or met-enkephalin content but resulted in a significant increase in NGF content. However, treatment of astrocytes in culture with met-enkephalin, morphine, or naltrexone had no effect on any of these parameters. No opiate binding could be detected, using either etorphine or bremazocine, to membranes of astrocytes prepared from cortex, cerebellum, striatum, or hippocampus of 1-day, 7-day, or 14-day postnatal rats. Thus we conclude that type 1 astrocytes do not express opiate receptors and that the in vivo effects of naltrexone are mediated indirectly via some other cell type/receptor.
Schwartz
J P
JP
Molecular Genetics Section, NINDS, NIH, Bethesda, Maryland 20892.
Nishiyama
N
N
Wilson
D
D
Taniwaki
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001575:Benzomorphans / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000254:growth & development; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005048:Etorphine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001575:Benzomorphans; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011943:Receptors, Adrenergic, beta; D011957:Receptors, Opioid; D005048:Etorphine; D004744:Enkephalin, Methionine; D009271:Naltrexone; C021717:enkephalin, Met(2)-ProNH2(5)-; D009020:Morphine; C027248:bremazocine