ABSTRACT
Vascular endothelial growth factors (VEGFs), a family of angiogenic factors, are upregulated by nerve injuries. To clarify the extracellular signals involved in VEGF production in the brain, the effects of endothelins (ETs), a family of vasoconstricting peptides, were examined. I.c.v. administration of 500 pmol/d Ala(1,3,11,15)-ET-1, an ET(B) receptor agonist, increased the level of VEGF-A mRNA in the rat cerebrum, whereas those of VEGF-B, placental growth factor (PLGF), angiopoietin (ANG)-1, and ANG-2 mRNAs were not largely affected by Ala(1,3,11,15)-ET. The ET-induced increases in cerebrum VEGF-A mRNA were reduced by coadministration of 1 nmol/d BQ788, an ET(B) antagonist. Ala(1,3,11,15)-ET-1 also stimulated the production of VEGF-A proteins in the cerebrum. Immunohistochemical observations in the cerebrum of Ala(1,3,11,15)-ET-1-infused rats showed that glial fibrillary acidic protein (GFAP)-positive astrocytes had VEGF-A immunoreactivity. Neurons, microglia, and brain capillary endothelial cells in the Ala(1,3,11,15)-ET-1-infused rats did not show VEGF-A reactivity. The i.c.v. administration of Ala(1,3,11,15)-ET-1 stimulated tyrosine phosphorylations of VEGF-R1 and R2 receptors in the rat cerebrum, whereas expression levels of total VEGF-R1 and R2 proteins were not largely changed. Immunoreactivity of tyrosine-phosphorylated VEGF-R1 was selectively shown in GFAP-positive astrocytes in the cerebrum of Ala(1,3,11,15)-ET-1-infused rats. Tyrosine-phosphorylated VEGF-R2 proteins were present in astrocytes and brain capillary endothelial cells. These findings indicate that activation of brain ET(B) receptors increases production of VEGF-A and stimulates VEGF receptor signaling in the brain.
Subject(s)
Brain/metabolism , Endothelin-1/administration & dosage , Receptor, Endothelin B/agonists , Receptors, Vascular Endothelial Growth Factor/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Brain/drug effects , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation/drug effects , Injections, Intraventricular , Male , RNA, Messenger/analysis , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
The aim of the present study was to investigate the pharmacological properties of the crude lyophilized extract (EBPC) of Paullinia cupana seeds (guaraná) and the semi-purified extracts (EPA and EPB) after acute or chronic administration by the oral route in rats. Anxiolytic-like, antidepressant-like and motor stimulant effects were evaluated using the plus maze (PMT), forced swimming (FST) and open field (OFT) tests, respectively. Acute or chronic administration of EBPC (3.0, 30.0 or 60.0 mg/kg) did not alter the percentage of entries or the time spent in the open arm in the PMT. In the FST, chronic treatment with 30.0 mg EBPC/kg and 4.0 mg EPA/kg extract decreased the immobility time similarly to the antidepressant reference drug, imipramine (20.0 mg/kg). Locomotor activity in the OFT was not increased by these extracts. Caffeine (10.0 mg/kg) significantly reduced the immobility time in the FST, but increased locomotor activity in the OFT, indicating psychostimulant activity. The EPB extract did not induce any effect after acute or chronic treatment in the different models used. The present results suggest that the crude EBPC extract and EPA extract produced an antidepressant-like effect after long-term administration.
Subject(s)
Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Paullinia/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , Animals , Antidepressive Agents/chemistry , Dose-Response Relationship, Drug , Freeze Drying , Male , Maze Learning/drug effects , Motor Activity/drug effects , Plant Extracts/chemistry , Rats , Rats, WistarABSTRACT
O objetivo deste trabalho foi o de avaliar o desempenho de 211 porcas da linhagem Camborough 22 Marca Registrada, de diferentes ordens de parto, submetidas à infusäo transcervical de plasma seminal ou de estrógeno no início do estro. Após o desmame, elas foram examinadas duas vezes ao dia para a detecçäo do estro, na presença de um macho sexualmente maduro, e da ovulaçäo, com auxílio da ultrasonografia transcutânea. No início do estro as fêmeas receberam aleatoriamente uma infusäo transcervical de plasma seminal, de estrógeno ou permaneceram como grupo-controle. Todas as fêmeas foram inseminadas no turno seguinte à detecçäo do estro, recebendo no máximo três inseminaçöes com intervalos de 8 a 16h. No grupo-controle as fêmeas de primeiro parto ovularam mais precocemente que as fêmeas com maior número de partos (P<0,05). Os tratamentos näo influenciaram a duraçäo do estro e o momento da ovulaçäo. O número total de leitöes nascidos näo diferiu entre os tratamentos