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Comprehensive Physiology

Rodger A Liddle
Even the simplest animals possess sophisticated systems for sensing and securing nutrients. After all, ensuring adequate nutrition is essential for sustaining life. Once multicellular animals grew too large to be nourished by simple diffusion of nutrients from their environment, they required a digestive system for the absorption and digestion of food. The majority of cells in the digestive tract are enterocytes that are designed to absorb nutrients. However, the digestive tracts of animals ranging from worms to humans contain specialized cells that discriminate between nutrients and nondigestible ingestants...
June 18, 2018: Comprehensive Physiology
Nhung T Nguyen, Weidong Han, Wen-Ming Cao, Youjun Wang, Shufan Wen, Yun Huang, Minyong Li, Lupei Du, Yubin Zhou
The calcium release-activated calcium (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), represents a prototypical example of store-operated calcium entry in mammals. The ORAI-STIM signaling occurs at membrane contact sites formed by close appositions between the endoplasmic reticulum (ER) and the plasma membrane. ORAI1 is a four-pass transmembrane protein that forms a highly calcium-selective ion channel in the plasma membrane. STIM1 is an ER-resident, a single-pass transmembrane protein that serves as a calcium sensor within the ER lumen and a potent activator of ORAI1 calcium channels...
June 18, 2018: Comprehensive Physiology
David A Rubenstein, Wei Yin
This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment...
June 18, 2018: Comprehensive Physiology
Uwe Proske, Simon C Gandevia
The kinesthetic senses are the senses of position and movement of the body, senses we are aware of only on introspection. A method used to study kinesthesia is muscle vibration, which engages afferents of muscle spindles to trigger illusions of movement and changed position. When vibrating elbow flexors, it generates sensations of forearm extension, when vibrating extensors, sensations of forearm flexion. Vibrating the elbow joint produces no illusion. Vibrating flexors and extensors together at the same frequency also produces no illusion, because what is perceived is the signal difference between antagonist muscles of each arm and between arms...
June 18, 2018: Comprehensive Physiology
David O Bates, Nicholas Beazley-Long, Andrew V Benest, Xi Ye, Nikita Ved, Richard P Hulse, Shaney Barratt, Maria J Machado, Lucy F Donaldson, Steven J Harper, Maria Peiris-Pages, Domingo J Tortonese, Sebastian Oltean, Rebecca R Foster
The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment...
June 18, 2018: Comprehensive Physiology
Nati Hernando, Carsten A Wagner
States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH)2 vitamin D3 , and dietary phosphate...
June 18, 2018: Comprehensive Physiology
Han Fang, Robert L Judd
Adipose tissue is now recognized as an important endocrine organ, capable of secreting a large number of endocrine factors which regulate a wide variety of physiological functions. Adiponectin is one such factor, secreted in large quantities primarily from adipose tissue. Adiponectin is posttranslationally modified from a 30-kDa monomeric protein into different multimers (low molecular weight or trimer, middle molecular weight or hexamer, and high molecular weight) and secreted into the circulation. Upon binding to its receptors, AdipoR1 and R2, adiponectin initiates a series of tissue-dependent signal transduction events, including phosphorylation of adenosine monophosphate (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK), and increased peroxisome proliferator-activated receptor alpha (PPARα) ligand activity...
June 18, 2018: Comprehensive Physiology
Medha Priyadarshini, Kumar U Kotlo, Pradeep K Dudeja, Brian T Layden
Nutrient sensing is a mechanism for organisms to sense their environment. In larger animals, including humans, the intestinal tract is a major site of nutrient sensing for the body, not surprisingly, as this is the central location where nutrients are absorbed. In the gut, bacterial fermentation results in generation of short chain fatty acids (SCFAs), a class of nutrients, which are sensed by specific membrane bound receptors, FFA2, FFA3, GPR109a, and Olfr78. These receptors are expressed uniquely throughout the gut and signal through distinct mechanisms...
June 18, 2018: Comprehensive Physiology
Patricia L Brubaker
Glucagon-like peptide-2 (GLP-2) is an intestinally derived hormone that enhances intestinal growth, digestion, absorption, barrier function, and blood flow in healthy animals as well as preventing damage and improving repair in preclinical models of enteritis and colitis and following massive small bowel resection. These beneficial effects of GLP-2 on the intestinal tract are largely recapitulated in humans with intestinal failure. The high-specificity of this peptide for the intestinal tract and the development of degradation-resistant, long-acting GLP-2 receptor agonists have rapidly led to clinical implementation of GLP-2-based therapy for the treatment of patients with short bowel syndrome, with few reported side effects...
June 18, 2018: Comprehensive Physiology
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June 18, 2018: Comprehensive Physiology
Peter Bie
Natriuretic peptides are structurally related, functionally diverse hormones. Circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are delivered predominantly by the heart. Two C-type natriuretic peptides (CNPs) are paracrine messengers, notably in bone, brain, and vessels. Natriuretic peptides act by binding to the extracellular domains of three receptors, NPR-A, NPR-B, and NPR-C of which the first two are guanylate cyclases. NPR-C is coupled to inhibitory proteins. Atrial wall stress is the major regulator of ANP secretion; however, atrial pressure changes plasma ANP only modestly and transiently, and the relation between plasma ANP and atrial wall tension (or extracellular volume or sodium intake) is weak...
June 18, 2018: Comprehensive Physiology
Jay Hegdé
The last three decades have seen major strides in our understanding of neural mechanisms of high-level vision, or visual cognition of the world around us. Vision has also served as a model system for the study of brain function. Several broad insights, as yet incomplete, have recently emerged. First, visual perception is best understood not as an end unto itself, but as a sensory process that subserves the animal's behavioral goal at hand. Visual perception is likely to be simply a side effect that reflects the readout of visual information processing that leads to behavior...
June 18, 2018: Comprehensive Physiology
Marçal Pastor-Anglada, Nerea Urtasun, Sandra Pérez-Torras
The gastrointestinal tract is the absorptive organ for nutrients found in foods after digestion. Nucleosides and, to a lesser extent nucleobases, are the late products of nucleoprotein digestion. These metabolites are absorbed by nucleoside (and nucleobase) transporter (NT) proteins. NTs are differentially distributed along the gastrointestinal tract showing also polarized expression in epithelial cells. Concentrative nucleoside transporters (CNTs) are mainly located at the apical side of enterocytes, whereas equilibrative nucleoside transporters (ENTs) facilitate the basolateral efflux of nucleosides and nucleobases to the bloodstream...
June 18, 2018: Comprehensive Physiology
Vincenza Cifarelli, Nada A Abumrad
Several proteins have been implicated in fatty acid (FA) transport by enterocytes including the scavenger receptor CD36 (SR-B2), the scavenger receptor B1 (SR-B1) a member of the CD36 family and the FA transport protein 4 (FATP4). Here, we review the regulation of enterocyte FA uptake and its function in lipid absorption including prechylomicron formation, assembly and transport. Emphasis is given to CD36, which is abundantly expressed along the digestive tract of rodents and humans and has been the most studied...
March 26, 2018: Comprehensive Physiology
Hua Xu, Fayez K Ghishan, Pawel R Kiela
The Slc9 family of Na+ /H+ exchangers (NHEs) plays a critical role in electroneutral exchange of Na+ and H+ in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins contribute to the transepithelial Na+ and water absorption, intracellular pH and cellular volume regulation as well as the electrolyte, acid-base, and fluid volume homeostasis at the systemic level. They also influence the function of other membrane transport mechanisms, affect cellular proliferation and apoptosis as well as cell migration, adherence to the extracellular matrix, and tissue repair...
March 26, 2018: Comprehensive Physiology
Adam Russell-Hallinan, Chris J Watson, John A Baugh
Remodeling of cardiac tissue architecture is essential for normal organ development and maintaining homeostasis after injury. Injurious insults to the heart, such as hypertension and myocardial infarction, promote cellular responses including stimulation of resident inflammatory cells, activation of endothelial cells and recruitment of immune cells, hypertrophy of cardiomyocytes, and activation of fibroblasts. The physiological goal of this coordinated cellular response is to repair damaged tissue while maintaining or restoring cardiac contractile function...
March 26, 2018: Comprehensive Physiology
John R Fitz-Clarke
Breath-hold diving is practiced by recreational divers, seafood divers, military divers, and competitive athletes. It involves highly integrated physiology and extreme responses. This article reviews human breath-hold diving physiology beginning with an historical overview followed by a summary of foundational research and a survey of some contemporary issues. Immersion and cardiovascular adjustments promote a blood shift into the heart and chest vasculature. Autonomic responses include diving bradycardia, peripheral vasoconstriction, and splenic contraction, which help conserve oxygen...
March 25, 2018: Comprehensive Physiology
Robert Rodríguez-Roisin, Michael J Krowka, Alvar Agustí
This review concentrates on the determinants of gas exchange abnormalities in liver-induced pulmonary vascular disorders, more specifically in the hepatopulmonary syndrome. Increased alveolar-arterial O2 difference, with or without different levels of arterial hypoxemia, and reduced diffusing capacity represent the most characteristic gas exchange disturbances in the absence of cardiac and pulmonary comorbidities. Pulmonary gas exchange abnormalities in the hepatopulmonary syndrome are unique encompassing all three pulmonary factors determining arterial PO2 , that is, ventilation-perfusion imbalance, increased intrapulmonary shunt and oxygen diffusion limitation that, combined, interplay with two relevant nonpulmonary determinants, that is, increased total ventilation and high cardiac output...
March 25, 2018: Comprehensive Physiology
Britta Spanier, Florian Rohm
As the organ with one of the largest surface areas facing the environment and responsible for nutrient uptake, the small intestine expresses numerous transport proteins in its brush-border membrane for efficient absorption and supply of dietary macro- and micronutrients. The understanding of regulation and functional interplay of these nutrient transporters is of emerging interest in nutrition and medical physiology research in respect to development of diabetes, obesity, and inflammatory bowel disease worldwide...
March 25, 2018: Comprehensive Physiology
David R Harder, Kevin R Rarick, Debebe Gebremedhin, Susan S Cohen
There have been numerous reviews related to the cerebral circulation. Most of these reviews are similar in many ways. In the present review, we thought it important to provide an overview of function with specific attention to details of cerebral arterial control related to brain homeostasis, maintenance of neuronal energy demands, and a unique perspective related to the role of astrocytes. A coming review in this series will discuss cerebral vascular development and unique properties of the neonatal circulation and developing brain, thus, many aspects of development are missing here...
March 25, 2018: Comprehensive Physiology
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