VIP-MEDIATED INCREASE IN CAMP PREVENTS TETRODOTOXIN-INDUCED RETINAL GANGLION-CELL DEATH INVITRO

被引:73
作者
KAISER, PK
LIPTON, SA
机构
[1] CHILDRENS HOSP MED CTR, DEPT NEUROL,CELLULAR & MOLEC NEUROSCI,ENDERS BLDG, ROOM 350, BOSTON, MA 02115 USA
[2] BETH ISRAEL HOSP, DEPT NEUROL, BOSTON, MA 02215 USA
[3] BRIGHAM & WOMENS HOSP, DEPT NEUROL, BOSTON, MA 02115 USA
[4] HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA
关键词
D O I
10.1016/0896-6273(90)90173-D
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Afferent influences on natural cell death were modeled in retinal cultures derived from neonatal rats. Tetrodotoxin (TTX) blockade of electrical activity produced a significant reduction in surviving retinal ganglion cell (RGC) neurons during a critical period of development, similar in magnitude to the reduction observed during natural cell death in the intact retina at a similar developmental stage. The addition of vasoactive intestinal peptide (VIP) protected the RGCs from the lethal action of TTX. This effect was specific, since the related peptides PHI-27 and secretin produced no significant increase in RGC survival. Radioimmunoassay of cyclic nucleotides showed that TTX decreased culture levels of cAMP and that this trend was reversed by VIP Decreases in RGC survival associated with TTX electrical blockade were prevented by 8-bromo:cAMP or forskolin. Furthermore, VIP10-28, the C-terminal fragment that inhibits VIP stimulation of adenylate cyclase, reduced the number of surviving RGCs. Thus, our results suggest that VIP, acting by increasing cAMP, has a neurotrophic effect on electrically blocked RGCs and may be an endogenous factor modulating normal cell death in the retina. © 1990.
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页码:373 / 381
页数:9
相关论文
共 54 条
[1]  
AMIRANOFF B, 1982, VASOACTIVE INTESTINA, P307
[2]   RECEPTORS FOR VASOACTIVE INTESTINAL PEPTIDE AND SECRETIN ON RAT PANCREATIC ACINI [J].
BISSONNETTE, BM ;
COLLEN, MJ ;
ADACHI, H ;
JENSEN, RT ;
GARDNER, JD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1984, 246 (06) :G710-G717
[3]  
Brecha N.C., 1985, P93
[4]  
BRENNEMAN DE, 1985, J PHARMACOL EXP THER, V233, P402
[5]   VASOACTIVE-INTESTINAL-PEPTIDE AND ELECTRICAL-ACTIVITY INFLUENCE NEURONAL SURVIVAL [J].
BRENNEMAN, DE ;
EIDEN, LE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (04) :1159-1162
[6]   NONNEURONAL CELLS MEDIATE NEUROTROPHIC ACTION OF VASOACTIVE-INTESTINAL-PEPTIDE [J].
BRENNEMAN, DE ;
NEALE, EA ;
FOSTER, GA ;
DAUTREMONT, SW ;
WESTBROOK, GL .
JOURNAL OF CELL BIOLOGY, 1987, 104 (06) :1603-1610
[7]   PRENATAL DEVELOPMENT OF THE OPTIC PROJECTION IN ALBINO AND HOODED RATS [J].
BUNT, SM ;
LUND, RD ;
LAND, PW .
DEVELOPMENTAL BRAIN RESEARCH, 1983, 6 (02) :149-168
[9]  
CLARKE PGH, 1981, PERSPECT BIOL MED, V25, P2
[10]   REGRESSIVE EVENTS IN NEUROGENESIS [J].
COWAN, WM ;
FAWCETT, JW ;
OLEARY, DDM ;
STANFIELD, BB .
SCIENCE, 1984, 225 (4668) :1258-1265