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Current Pharmaceutical Design 2012Renin-angiotensin-aldosterone (RAAS) is a hormone system which acts on multiple physiologic pathways primarily by regulating blood pressure and fluid balance, but also... (Review)
Review
Renin-angiotensin-aldosterone (RAAS) is a hormone system which acts on multiple physiologic pathways primarily by regulating blood pressure and fluid balance, but also by local autocrine and paracrine actions. In pathophysiologic conditions RAAS also contributes to the development of atherosclerosis and its various manifestations, both directly and indirectly through the actions on other systems. RAAS mainly acts as a promoter of atherosclerosis by its action on vessels, and by promoting the development of hypertension, insulin resistance and diabetes, obesity, vascular and systemic inflammation. As RAAS plays a key role in the pathogenesis of cardiovascular diseases, RAAS genes have been extensively studied as candidate genes for atherosclerosis and coronary artery disease. Several polymorphisms of its genes have been found to be in relationship with atherosclerosis and cardiovascular diseases. In this review we will discuss these issues and present the most recent advances about this topic.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Humans; Renin-Angiotensin System
PubMed: 22283771
DOI: 10.2174/138161212799436467 -
Clinical and Experimental Pharmacology... Aug 2017Neurotensin (NTS) has long been recognized as a neurotransmitter or neuromodulator in the central nervous system and as an endocrine agent in the periphery via actions... (Review)
Review
Neurotensin (NTS) has long been recognized as a neurotransmitter or neuromodulator in the central nervous system and as an endocrine agent in the periphery via actions mediated through neurotensin receptors (NTSRs). Many studies support a role for NTS in the endocrine, autocrine and paracrine growth stimulation of cancer, with oncogenic actions described for NTS in different types of cancers and cancer cell lines at each step of cancer progression, ranging from tumour growth and survival to metastatic spread. The mechanisms underlying the effects of the NTS/NTSR system in cell proliferation, migration and invasion, as well as the anti-apoptotic effects of this system, have been elucidated in different types of cancers, and include mitogen-activated protein kinases, phosphatidylinositol 3-kinase and RhoGTPases. The present mini review summarizes recent findings relating to the oncogenic function of the NTS/NTSR system.
Topics: Animals; Carcinogenesis; Humans; Neoplasms; Neurotensin; Receptors, Neurotensin; Signal Transduction
PubMed: 28556374
DOI: 10.1111/1440-1681.12787 -
Seminars in Cell & Developmental Biology Jul 2016The past decade has borne witness to an explosion in our understanding of the fundamental complexities of intercellular communication. Previously, the field was solely... (Review)
Review
The past decade has borne witness to an explosion in our understanding of the fundamental complexities of intercellular communication. Previously, the field was solely defined by the simple exchange of endocrine, autocrine and epicrine agents. Then it was discovered that cells possess an elaborate system of extracellular vesicles, including exosomes, which carry a vast array of small and large molecules (including many epigenetic agents such as a variety RNAs and DNA), as well as large organelles that modulate almost every aspect of cellular function. In addition, it was thought that electrical communication between cells was limited mainly to neurotransmitters and neuromodulators in the nervous system. Also within the past decade, it was found that - in addition to neurons - most cells (both mammalian and non-mammalian) communicate via elaborate bioelectric systems which modulate many fundamental cellular processes including growth, differentiation, morphogenesis and repair. In the nervous system, volume transmission via the extracellular matrix has been added to the list. Lastly, it was discovered that what had previously been regarded as simple connective cells in most tissues proved to be miniature communication devices now known as telocytes. These unusually long, tenuous and sinuous cells utilize elaborate electrical, chemical and epigenetic mechanisms, including the exchange of exosomes, to integrate many activities within and between nearly all types of cells in tissues and organs. Their interrelationship with neural stem cells and neurogenesis in the context of neurodegenerative disease is just beginning to be explored. This review presents an account of precisely how each of these varied mechanisms are relevant and critical to the understanding of what telocytes are and how they function.
Topics: Animals; Brain; Cell Communication; Electrophysiological Phenomena; Humans; Neurodegenerative Diseases; Telocytes
PubMed: 27013113
DOI: 10.1016/j.semcdb.2016.03.010 -
Annals of the New York Academy of... Jun 2003The interest in the physiological role of alpha-MSH in birds has been limited because they lack the intermediate lobe of the pituitary, the main source of circulating... (Review)
Review
The interest in the physiological role of alpha-MSH in birds has been limited because they lack the intermediate lobe of the pituitary, the main source of circulating alpha-MSH in most vertebrates. Recent studies have improved our understanding of the avian melanocortin system. We have cloned and characterized all five MC-R subtypes, POMC, and AGRP in chicken. Analyses of the tissue distribution of expression of these genes revealed widespread expression throughout the body, corresponding to the situation in mammals in which alpha-MSH exerts a multiplicity of effects in different tissues by acting as a local mediator. We showed that the extended black locus controlling feather pigmentation in the chicken encodes MC1-R. Moreover, black chickens carrying the dominant allele, the extended black, express the MC1-R with ligand-independent activity as the somber-3J black mice. alpha-MSH and AGRP were expressed in the infundibular nucleus of POMC and NPY neurons, respectively, in the brain of Japanese quail. Furthermore, fasting stimulated AGRP expression and lowered POMC expression. These data indicate that at least two of the major melanocortin systems reported in mammals, that is, regulation of pigmentation and energy homeostasis, was developed in a common ancestor to chicken and mammals at least 300 million years ago. Furthermore, alpha-MSH peptide was identified in developing chicken eye, suggesting a possible involvement of alpha-MSH in regulation of ocular development. Collectively, the data reviewed here indicate that alpha-MSH is produced locally and acts as an autocrine/paracrine hormone in birds.
Topics: Animals; Autocrine Communication; Birds; Energy Metabolism; Eye; Homeostasis; Paracrine Communication; Pigmentation; Receptors, Corticotropin; Receptors, Melanocortin; alpha-MSH
PubMed: 12851337
DOI: 10.1111/j.1749-6632.2003.tb03201.x -
Cellular and Molecular Life Sciences :... Jun 2008Galanin has diverse physiological functions, including nociception, arousal/sleep regulation, cognition, and many aspects of neuroendocrine activities that are... (Review)
Review
Galanin has diverse physiological functions, including nociception, arousal/sleep regulation, cognition, and many aspects of neuroendocrine activities that are associated with feeding, energy metabolism, thermoregulation, osmotic and water balance, and reproduction. This review will provide a brief overview of galanin actions in some major neuroendocrine processes. Most of the recent data are about the role of galanin in the central regulation of food intake and energy metabolism, and to some extent, in the regulation of reproduction. It seems that galanin plays a modulatory rather than regulatory role in the central and peripheral branches of the neuroendocrine systems. In the hypothalamus, it functions as a neurotransmitter/neuromodulator. In the pituitary and the peripheral endocrine glands, it acts via its receptors (GALRs) in a paracrine/autocrine fashion. The development of new, selective and potent antagonists of GALRs should keep advancing our knowledge not only in the physiology but also the pathophysiology of galanin as well.
Topics: Animals; Drinking; Eating; Energy Metabolism; Galanin; Gonads; Growth Hormone; Hypothalamo-Hypophyseal System; Hypothalamus; Pituitary-Adrenal System; Prolactin; Thyrotropin
PubMed: 18500643
DOI: 10.1007/s00018-008-8157-4 -
Archives of Internal Medicine Apr 1993The renin-angiotensin system traditionally has been conceived as a neuroendocrine system functioning in the circulation. Recent research has confirmed the existence of... (Review)
Review
The renin-angiotensin system traditionally has been conceived as a neuroendocrine system functioning in the circulation. Recent research has confirmed the existence of autocrine/paracrine tissue renin-angiotensin systems present and functioning at multiple sites, including cardiac, vascular, and renal tissues, which contain the majority of angiotensin-converting enzyme in the body. It appears that the circulating renin-angiotensin system is activated acutely to maintain homeostasis and is then turned off at cardiovascular compensation, while the tissue renin-angiotensin systems exert long-term actions that affect cardiovascular function and structure, which may play a pathophysiological role in congestive heart failure, hypertension, and vascular disease and influence the response to therapy with angiotensin-converting enzyme-inhibiting agents.
Topics: Animals; Cardiomegaly; Heart Failure; Humans; Peptidyl-Dipeptidase A; Renin-Angiotensin System
PubMed: 8386920
DOI: No ID Found -
Current Biology : CB Mar 2018Many receptor-like kinases localized at the pollen tube tip precisely control tube functions in flowering plants. Two recent reports have identified autocrine peptide...
Many receptor-like kinases localized at the pollen tube tip precisely control tube functions in flowering plants. Two recent reports have identified autocrine peptide ligands and receptor systems, providing insight into the molecular machinery that controls pollen tube growth and termination.
Topics: Arabidopsis; Arabidopsis Proteins; Genes, Plant; Peptides; Pollen Tube
PubMed: 29558643
DOI: 10.1016/j.cub.2018.01.067 -
The American Journal of Cardiology Oct 1992At the cellular and molecular level the transition to heart failure is a complex process that involves structural adaptation, not only of the heart, but of peripheral... (Review)
Review
At the cellular and molecular level the transition to heart failure is a complex process that involves structural adaptation, not only of the heart, but of peripheral vasculature and renal tissues as well. Recent studies have suggested that autocrine, paracrine, and circulating biologically active mediators activate events that result in the concerted failure of adaptive mechanisms and the ultimate depression of cardiac myocyte function. Greater understanding of these local mechanisms in the future may lead to drug therapies that can selectively block these mechanisms and prevent the progression from compensation to overt heart failure.
Topics: Cardiomegaly; Heart; Heart Failure; Humans; Neurosecretory Systems; Neurotransmitter Agents
PubMed: 1357950
DOI: 10.1016/0002-9149(92)91352-5 -
Nature Clinical Practice. Nephrology Feb 2009Evidence suggests that virtually every organ system in the human body possesses a local renin-angiotensin system (RAS). These local systems seem to be independently... (Review)
Review
Evidence suggests that virtually every organ system in the human body possesses a local renin-angiotensin system (RAS). These local systems seem to be independently regulated and compartmentalized from the plasma circulation, perhaps with the exception of the vascular endothelial system, which is responsible for maintaining physiological plasma levels of RAS components. Among these local RASs, the kidney RAS--the focus of this Review--seems to be of critical importance for the regulation of blood pressure and salt balance. Indeed, overactivation of the intrarenal RAS in certain disease states constitutes a pathogenic mechanism that leads to tissue injury, proliferation, fibrosis and ultimately, end-organ damage. Intrarenal levels of angiotensin peptides are considerably higher than those in plasma or any other organ tissue. Moreover, the kidney has a unique capacity to degrade angiotensin peptides, perhaps to maintain its intrinsic homeostasis. Interestingly, each local RAS has a distinct enzymatic profile resulting in different patterns of angiotensin fragment generation in different tissues. A better understanding of the autocrine and paracrine mechanisms involved in the renal RAS and other local RASs might direct future organ-specific therapy.
Topics: Animals; Humans; Kidney; Kidney Diseases; Renin-Angiotensin System
PubMed: 19065132
DOI: 10.1038/ncpneph1015 -
Biophysical Journal Oct 2001Autocrine loops formed by growth factors and their receptors have been identified in a large number of developmental, physiological, and pathological contexts. In...
Autocrine loops formed by growth factors and their receptors have been identified in a large number of developmental, physiological, and pathological contexts. In general, the spatially distributed and recursive nature of autocrine signaling systems makes their experimental analysis, and often even their detection, very difficult. Here, we combine Brownian motion theory, Monte Carlo simulations, and reaction-diffusion models to analyze the spatial operation of autocrine loops. Within this modeling framework, the ability of autocrine cells to recapture the endogenous ligand and the distances traveled by autocrine ligands are explicitly related to ligand diffusion coefficients, density of surface receptors, ligand secretion rate, and rate constants of ligand binding and endocytic internalization. Applying our models to study autocrine loops in the epidermal growth factor receptor system, we find that autocrine loops can be highly localized--even at the level of a single cell. We demonstrate how the variations in molecular and cellular parameters may "tune" the spatial range of autocrine signals over several orders of magnitude: from microns to millimeters. We argue that this versatile regulation of the spatial range of autocrine signaling enables autocrine cells to perceive a broad spectrum of environmental information.
Topics: Autocrine Communication; Diffusion; Epidermal Growth Factor; ErbB Receptors; Kinetics; Ligands; Models, Biological; Protein Binding; Receptors, Cell Surface; Signal Transduction
PubMed: 11566760
DOI: 10.1016/S0006-3495(01)75837-7