RESUMO
La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)
Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)
Assuntos
Humanos , Animais , Camundongos , Hormônios Neuro-Hipofisários/biossíntese , Arginina Vasopressina/efeitos adversos , Ocitocina/uso terapêutico , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese , Osteoporose/terapia , Hormônios Neuro-Hipofisários/fisiologia , Arginina Vasopressina/antagonistas & inibidores , Arginina Vasopressina/biossíntese , Arginina Vasopressina/fisiologia , Arginina Vasopressina/uso terapêutico , Ocitocina/biossíntese , Ocitocina/efeitos adversos , Ocitocina/fisiologia , Transdução de Sinais , Densidade Óssea , Densidade Óssea/efeitos dos fármacos , Receptores de Ocitocina/biossíntese , Receptores de Ocitocina/fisiologia , Estradiol/uso terapêutico , Estrogênios/fisiologiaRESUMO
The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.
Assuntos
Arginina Vasopressina/análise , Hipocampo/química , Hipotálamo Anterior/química , Fibras Nervosas Mielinizadas/química , Núcleo Hipotalâmico Paraventricular/química , Sinapses/química , Animais , Arginina Vasopressina/fisiologia , Hipocampo/fisiologia , Hipotálamo Anterior/fisiologia , Masculino , Fibras Nervosas Mielinizadas/fisiologia , Vias Neurais/química , Vias Neurais/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Wistar , Sinapses/fisiologiaRESUMO
We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina , Arginina Vasopressina/antagonistas & inibidores , Receptores de Vasopressinas/administração & dosagem , Sódio/metabolismo , Angiotensina II/antagonistas & inibidores , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Pressão Sanguínea , Relação Dose-Resposta a Droga , Hipotálamo/metabolismo , Injeções Intraventriculares , Losartan/farmacologia , Masculino , Oligopeptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Angiotensina/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: The aim of this work was to study the effects of low intensity laser radiation on water transport in the toad bladder in vitro. STUDY DESIGN/MATERIALS AND METHODS: The water flow through the membrane was measured gravimetrically in bag preparations of the membrane. RESULTS: Laser radiation did not alter the water transport in the presence nor in the absence of vasopressin. In contrast, when the hemibladders were previously treated with vasopressin, the laser decreased by approximately 33.70% arginine-vasopressin (AVP)-mediated water transport. Laser radiation increased 3'5'-cyclic adenosine monophosphate (3'5'-cAMP) mediated water transport by approximately 23%. The association of laser radiation with indomethacin (IND) did not affect AVP-mediated water transport. CONCLUSIONS: This data suggests that the laser may have two effects on AVP-mediated water transport: one inhibitory effect on 3'5'-cAMP synthesis by inhibiting the adenylate cyclase complex and another stimulatory effect by inhibiting nucleotide-phosphodiesterase activity. Our results also indicate that the laser does not interfere in the prostaglandins biosynthesis induced by AVP.
Assuntos
Terapia com Luz de Baixa Intensidade , Bexiga Urinária/efeitos da radiação , Animais , Arginina Vasopressina/fisiologia , Transporte Biológico/efeitos da radiação , Bufo marinus , Indometacina/farmacologia , Masculino , Equilíbrio Hidroeletrolítico/efeitos da radiaçãoRESUMO
Arginine vasopressin (AVP) is a nonapeptide long known as an endocrine and paracrine regulator of important systemic functions, namely, vasoconstriction, gluconeogenesis, corticosteroidogenesis, and excretion of water and urea. Here we report, for the first time, that AVP specifically inhibits expression of the cyclin D1 gene, leading to cell cycle blockage and halting cell proliferation. In G0/G1-arrested mouse Y1 adrenocortical tumor cells, maintained in serum-free medium (SFM), AVP mimics FGF2, promoting rapid ERK1/2 activation (5 min) followed by c-Fos protein induction (2 h). PKC inhibitor Go6983 and PI3K inhibitors wortmannin and LY294002 all inhibit ERK1/2 activation by AVP, but not by FGF2. Thus, AVP and FGF2 concur to activate ERK1/2 by different regulatory pathways. However, AVP is not a mitogenic factor for Y1 cells. On the contrary, AVP strongly antagonizes FGF2 late induction (2-5 h) of the cyclin D1 gene, down-regulating both cyclin D1 mRNA and protein. AVP inhibition of cyclin D1 expression is sufficient to block G1 phase progression and cell entry into the S phase, monitored by BrdU nuclear labeling. In addition, AVP completely inhibits proliferation of Y1 cells in 10% fetal calf serum (10% FCS) medium. On the other hand, ectopic expression of the cyclin D1 protein renders Y1 cells resistant to AVP for both entry into the S phase in SFM and continuous proliferation in 10% FCS medium. In conclusion, inhibition of cyclin D1 expression by AVP is an efficient mechanism of cell cycle blockage and consequent proliferation inhibition in Y1 adrenocortical cells.
Assuntos
Arginina Vasopressina/fisiologia , Ciclo Celular/fisiologia , Ciclina D1/antagonistas & inibidores , Ciclina D1/biossíntese , Regulação da Expressão Gênica/fisiologia , Inibidores do Crescimento/fisiologia , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologia , Neoplasias do Córtex Suprarrenal/enzimologia , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Animais , Arginina Vasopressina/farmacologia , Ciclo Celular/efeitos dos fármacos , Células Clonais , Meios de Cultivo Condicionados , Ciclina D1/genética , Resistencia a Medicamentos Antineoplásicos , Ativadores de Enzimas/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fase G1/efeitos dos fármacos , Fase G1/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mimetismo Molecular , Fosfatidilinositol 3-Quinases/fisiologia , Proteína Quinase C/fisiologia , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/fisiologia , Transfecção , Células Tumorais Cultivadas/enzimologiaRESUMO
The presence of both CFTR and ClC-2 proteins in the kidney suggest that they are involved in chloride transport along the nephron but their physiological roles in this organ are not known. To further understand the role of these chloride channels we studied Wistar rats subjected to dehydration for 2 days and also the homozygous Brattleboro rats, a strain of Long-Evans rats carrying an autosomal recessive mutation that leads to a deficiency of arginine-vasopressin (AVP) secretion in the plasma. The expression of CFTR was increased in the medulla of dehydrated Wistar rats and no variation was observed in the cortex. The expression of both ClC-2 and CFTR mRNAs was low in the renal cortex and medulla of the homozygous Brattleboro rats but returned to normal levels after AVP reposition. By the use of Madine-Darby canine kidney (MDCK) type I epithelial cells, it was observed that AVP (10(-8), 10(-7) and 10(-6) M) increased CFTR mRNA expression "in vitro" but no effect was observed when changes in the medium tonicity were caused by the addition of sucrose, NaCl, manitol or urea. The modulation of both CFTR and ClC-2 mRNA by AVP, the main hormone involved in the regulation of body fluid osmolality, suggests the participation of these two chloride channels in the renal tubule transcellular chloride transport modulated by AVP.
Assuntos
Arginina Vasopressina/fisiologia , Canais de Cloreto/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Medula Renal/metabolismo , Animais , Sangue/metabolismo , Western Blotting , Canais de Cloro CLC-2 , Linhagem Celular , Desidratação/metabolismo , Cães , Homozigoto , Rim/metabolismo , Córtex Renal/metabolismo , Concentração Osmolar , RNA Mensageiro/metabolismo , Ratos , Ratos Brattleboro/genética , Ratos Long-Evans , Ratos Wistar , Receptores de Vasopressinas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Urina/químicaRESUMO
O diabetes insipidus nefrogênico (DIN) é uma doença rara caracterizada pela incapacidade do rim de concentrar a urina, a despeito de concentrações normais ou aumentadas do hormônio antidiurético arginina-vasopressina (AVP). Recentes avanços da fisiopatologia renal mostraram que, após a ligação do AVP ao seu receptor AVPR2 (receptor de vasopressina tipo 2), uma cascata de eventos culmina com a reabsorção de água no túbulo coletor, por meio de canais permeáveis exclusivamente à água e localizados nas membranas apicais do túbulo coletor, sendo o mais importante deles a aquaporina-2 (AQP2). A identificação, caracterização e análise mutacional dos genes AVPR2 e AQP2 permitiram estabelecer as bases moleculares de vários tipos hereditários de diabetes insipidus nefrogênico. Aproximadamente 90 por cento desses pacientes apresentam mutações do AVPR2, 8 por cento apresentam mutações no AQP2 e o restante não tem causas identificadas. Nessa revisão apresentamos exemplos de alterações genéticas e sugerimos que o uso de técnicas de biologia molecular pode minimizar as complicações dessa doença heterogênea mas com fenótipo bastante semelhante.
Assuntos
Humanos , Masculino , Feminino , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/fisiopatologia , Aquaporinas/genética , Arginina Vasopressina/fisiologia , Diabetes Insípido Nefrogênico/genética , Mutação , Linhagem , Receptores de Vasopressinas/genéticaRESUMO
Vasopressin and bradykinin are two of the most important peptides in regulating vascular tone, water, and ionic balance in the body, and thus they play a key role in controlling blood pressure. In addition to being a potent vasoconstrictor, Vasopressin also has an antidiuretic activity in the kidney, whereas kinins regulate renal blood flow in addition to their vasodilatory and natriuretic activity. We review here the primary evidence for the localization of the vasopressin and kinin receptors and their role in ionic and water regulation in the kidney.
Assuntos
Arginina Vasopressina/fisiologia , Túbulos Renais/metabolismo , Receptores da Bradicinina/fisiologia , Receptores de Vasopressinas/fisiologia , Animais , Humanos , Sistema Calicreína-Cinina/fisiologia , Cininas/metabolismo , Potássio/metabolismo , Sódio/metabolismoRESUMO
Vasopressin and bradykinin are two of the most important peptides in regulating vascular tone, water, and ionic balance in the body, adn thus they play a key role in controlling blood pressure. In addition to being a potent vasoconstrictor, Vasopressin also has an antidiuretic activity in the kidney, whereas kinins regulate renal blood flow in addition to their vasodilatory and natriuretic activity. We review here the primary evidence for the localization of the vasopressin and kinin receptors and their role in ionic and water regulation in the kidney.
Assuntos
Humanos , Animais , Arginina Vasopressina/fisiologia , Túbulos Renais/metabolismo , Receptores da Bradicinina/fisiologia , Receptores de Vasopressinas/fisiologia , Sistema Calicreína-Cinina/fisiologia , Cininas/metabolismo , Potássio/metabolismo , Sódio/metabolismoRESUMO
It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08 degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19 degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0. 10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic injection of the AVP blocker [beta-mercapto-beta, beta-cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg) caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection of L-NAME caused an increase in Tb, but when intracerebroventricular L-NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.