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Glial proteins released by VIP: Neurodevelopmental significance
146
VIP INCREASES LOCAL VAGINAL SUBEPITHELIAL APPLICATION
BLOOD
FLOW
IN
WOMEN
AFTER
H. EJDRUP BREDKJ~ER I, C. PALLE I, B. OTTESEN 2, and J. FAHRENKRUG I, iDept, of Clinical Chemistry, Bispebjerg Hospital and 2Dept. of Gyn. & Obstet., Hvidovre Hospital, Copenhagen, Denmark. The effect of VIP on the vaginal blood flow was studied by the heated oxygen electrode. Peripheral blood samples were collected throughout the experiments for measurement of VIP by radioimmunoassay. Three setups were used: i) subepithelial (s.e.) injections of VIP in the following doses: 0, 0.i, i, 3, i0, 30 and 75 ~g. 2) Intravenous (i.v.) administration of VIP was given using the same doses as above except that 75 ~g was omitted. 3) s.e. a d m i n i s t r a t i o n of VIP in the same and the opposite site of the electrode to examine the influence of the site of injection. Both s.e. and i.v. injections induced a significantly dosedependent increase in local vaginal blood flow. The two dose response curves displayed the same potency and the effect of VIP was independent of the site of injection in the vagina. The flow values correlated with the corresponding plasma concentrations irrespective of the route of VIP administration, although the plasma levels after i.v. injections were higher. The present findings indicate that the effect of VIP on the vaginal blood flow is part of a systemic v a s o d i l a t o r y effect.
GLIAL PROTEINS RELEASED BY VIP: NEURODEVELOPMENTAL SIGNIFICANCE
D.E. Brenneman, Laboratory of Developmental Neurobiology, NICHD, NIH, Bethesda, Maryland USA The release of S35methionine-labeled proteins and neurotrophic substances after VIP treatment was measured in astroglial cultures derived from rat cerebral cortex. Previous studies indicated that nonneuronal cells mediate the neurotrophic action of VIP (J. Cell Biol. 104,1603, 1987). To investigate the glial proteins which may participate in this action, conditioned medium was collected after one hour incubations with 0.1 nM VIP. Two-dimensional polyacrylamide gel electrophoresis revealed an increase (> 50% of control) in 15 out of the 333 medium proteins. The proteins responding to VIP had molecular weights from 17 to 117 kDaltons and all had acidic pl's. By optical density, the VIPstimulated proteins comprised 18-22% of the total labeled protein released from the glial cultures. The three proteins showing greatest (9-25 fold) increase from controls were between 45 and 52 kDaltons. PHI-27 had no effect on any of the VIP-stimolated proteins. In addition, neurotrophic activity that increased neuronal survival of spinal cord neurons was detected in the glia-conditioned medium after VIP treatment, but not in medium from controls. The survival-promoting material was retained by polysulfone filtration with a molecular weight exclusion of 30 kDaltons. These data indicate that low concentrations of VIP release a complex mixture of glial proteins of high molecular weight, which include neurotrophlc substances important to neuronal survival during development.
VIP INCREASES LOCAL VAGINAL SUBEPITHELIAL APPLICATION
BLOOD
FLOW
IN
WOMEN
AFTER
H. EJDRUP BREDKJ~ER I, C. PALLE I, B. OTTESEN 2, and J. FAHRENKRUG I, iDept, of Clinical Chemistry, Bispebjerg Hospital and 2Dept. of Gyn. & Obstet., Hvidovre Hospital, Copenhagen, Denmark. The effect of VIP on the vaginal blood flow was studied by the heated oxygen electrode. Peripheral blood samples were collected throughout the experiments for measurement of VIP by radioimmunoassay. Three setups were used: i) subepithelial (s.e.) injections of VIP in the following doses: 0, 0.i, i, 3, i0, 30 and 75 ~g. 2) Intravenous (i.v.) administration of VIP was given using the same doses as above except that 75 ~g was omitted. 3) s.e. a d m i n i s t r a t i o n of VIP in the same and the opposite site of the electrode to examine the influence of the site of injection. Both s.e. and i.v. injections induced a significantly dosedependent increase in local vaginal blood flow. The two dose response curves displayed the same potency and the effect of VIP was independent of the site of injection in the vagina. The flow values correlated with the corresponding plasma concentrations irrespective of the route of VIP administration, although the plasma levels after i.v. injections were higher. The present findings indicate that the effect of VIP on the vaginal blood flow is part of a systemic v a s o d i l a t o r y effect.
GLIAL PROTEINS RELEASED BY VIP: NEURODEVELOPMENTAL SIGNIFICANCE
D.E. Brenneman, Laboratory of Developmental Neurobiology, NICHD, NIH, Bethesda, Maryland USA The release of S35methionine-labeled proteins and neurotrophic substances after VIP treatment was measured in astroglial cultures derived from rat cerebral cortex. Previous studies indicated that nonneuronal cells mediate the neurotrophic action of VIP (J. Cell Biol. 104,1603, 1987). To investigate the glial proteins which may participate in this action, conditioned medium was collected after one hour incubations with 0.1 nM VIP. Two-dimensional polyacrylamide gel electrophoresis revealed an increase (> 50% of control) in 15 out of the 333 medium proteins. The proteins responding to VIP had molecular weights from 17 to 117 kDaltons and all had acidic pl's. By optical density, the VIPstimulated proteins comprised 18-22% of the total labeled protein released from the glial cultures. The three proteins showing greatest (9-25 fold) increase from controls were between 45 and 52 kDaltons. PHI-27 had no effect on any of the VIP-stimolated proteins. In addition, neurotrophic activity that increased neuronal survival of spinal cord neurons was detected in the glia-conditioned medium after VIP treatment, but not in medium from controls. The survival-promoting material was retained by polysulfone filtration with a molecular weight exclusion of 30 kDaltons. These data indicate that low concentrations of VIP release a complex mixture of glial proteins of high molecular weight, which include neurotrophlc substances important to neuronal survival during development.