Effects of L-Arginine and α / 中国医学科学院学报

Kidney is one of the important organs of the body.With both excretory and endocrine functions,it plays a vital role in regulating the normal physiological state.As a precursor of the nitric oxide(NO)synthesis

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.

Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.

Evaluation of the role of melatonin in formalin-induced pain response in mice.

BACKGROUND: Melatonin, the major secretory product of pineal gland has been suggested to play a regulatory role in the circadian rhythm of body activities including the pain sensitivity. Three subtypes of melatonin receptors, i.e. ML1, ML2 and ML3 have been identified. AIM: To investigate the antinociceptive activity of melatonin and to unravel the underlying receptor mechanisms involved in this action. MATERIAL AND METHODS: Effect of melatonin (25-100 mg/kg, ip) and its interaction with putative melatonin receptor antagonists and opioidergic and serotoninergic agents have been studied in formalin test, a model of tonic continuous pain. Formalin (0.1 ml of 1% solution) was injected under the plantar surface of right hind paw of mice and the time an animal spent in licking the injected paw was measured. STATISTICAL ANALYSIS: The data were analysed by one-way ANOVA followed by Tukey's test for multiple comparisons. RESULTS: Injection of formalin produced two phases of intense licking, an early phase (0-5 min) and a late phase (20-25 min). Melatonin dose-dependently decreased the licking response in both the phases, effect being more marked in the late phase. Luzindole, a ML1 receptor antagonist did not block but rather enhanced the antinociceptive activity of melatonin. However, prazosin, a ML2 receptor antagonist in the low dose (0.5 mg/kg) significantly attenuated but in higher dose (1 mg/kg) enhanced the analgesic effect of melatonin. Naloxone, an opioid receptor antagonist did not reverse but morphine, an opioid agonist enhanced the antinociceptive activity of melatonin. Both mianserin and ondansetron the 5HT2 and 5HT3 receptor antagonists, respectively increased the analgesic effect of melatonin. CONCLUSION: The present results suggest the involvement of ML2 receptors in mediating the antinociceptive activity of melatonin in formalin-induced pain response. Further an interplay between melatonin, alpha-1 adrenergic and 5HT2 and 5HT3 serotoninergic receptors may also be participating in this action.

Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats

We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.

Important recent advances in cardiovascular adrenergic mechanisms

Five sub-areas were taken into consideration: Adrenoceptor subclassification: Presently, 10 different adrenoceptor subtypes have been characterized by pharmacological and molecular biology studies: Ó1A-, Ó1B-, Ó1D-, Ó2A/D, Ó2B-, Ó2C-, ß1-, ß2-, ß3- and ß4-adrenoceptors. Intracellular signaling: the adrenoceptors are members of a large superfamily of receptors linked to guanine-nucleotide proteins (G proteins), Ó1-adrenoceptors are coupled to Gq proteins and activate phospholipases, especially phospholipase Cß, Ó2-adrenoceptors are coupled to G1 proteins and inhibit adenylyl cyclase and in some tissues regulate potassium and calcium channels. Both ß1 and ß2-adrenoceptors are preferentially coupled to adenylyl cyclase through GS proteins and ß3-adrenoceptors appear to be coupled to K+ channel through a pertussis toxin-sensitive G1 protein. ß4-Adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo desensitization. Influence of maturation and ageing: From birth to old age important changes occur in animal models as in humans at the receptor level, neurotransmitter process and catecholamine disposition. In general terms, one can say that maturation is associated with a gradual increase of adrenergic influence, while ageing is associated with a reduction in the role of the adrenergic system on the regulation of physiologic processes. Cotransmission: ATP and the neuropeptide Y are cotransmitters with noradrenaline. While noradrenaline is the main transmitter in vascular tissues, ATP has functional relevance in some vessels and neuropeptide Y is mainly a modulator of noradrenaline release; it seems that it has an increased role under pathophysiological conditions like ischemia. Role of endothelium on noradrenaline release: Many substances produced by the endotelium or acting through the endothelium are able to influence noradrenaline release from sympathetic nerve varicosities of the blood vessel wall: some of them, like bradykinin and angiotensin II, exert a facilitatory, while others like NO and endothelin have an inhibitory effect on noradrenaline release evoked electrical nerve stimulation.