Abstract:
:This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.
journal_name
Physiol Revjournal_title
Physiological reviewsauthors
Brain SD,Grant ADdoi
10.1152/physrev.00037.2003subject
Has Abstractpub_date
2004-07-01 00:00:00pages
903-34issue
3eissn
0031-9333issn
1522-1210pii
84/3/903journal_volume
84pub_type
杂志文章,评审abstract::NHE3 is the brush-border (BB) Na(+)/H(+) exchanger of small intestine, colon, and renal proximal tubule which is involved in large amounts of neutral Na(+) absorption. NHE3 is a highly regulated transporter, being both stimulated and inhibited by signaling that mimics the postprandial state. It also undergoes downregu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00030.2006
更新日期:2007-07-01 00:00:00
abstract::Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions inclu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00041.2013
更新日期:2014-10-01 00:00:00
abstract::The life history of fibroblast and fibroblast-like cells includes an initial stage of outgrowth and establishment in culture; a period of vigorous proliferation which has a variable length, depending on the tissue of origin, age of the donor, etc.; a period of declining proliferative vigor which includes substantial c...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1993.73.3.617
更新日期:1993-07-01 00:00:00
abstract::The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the bas...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00015.2019
更新日期:2020-01-01 00:00:00
abstract::Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00042.2012
更新日期:2015-04-01 00:00:00
abstract::While transport processes for amino acids and glucose have long been known to be expressed in the luminal and abluminal membranes of the endothelium comprising the blood-brain and blood-retinal barriers, it is only within the last decades that endothelial and smooth muscle cells derived from peripheral vascular beds h...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00022.2002
更新日期:2003-01-01 00:00:00
abstract::Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibili...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00011.2002
更新日期:2002-10-01 00:00:00
abstract::The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for c...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00019.2008
更新日期:2009-01-01 00:00:00
abstract::The distal tubule of the mammalian kidney, defined as the region between the macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functional properties of individual cell types and has led to controversy concerning mechanisms and reg...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2000.80.1.277
更新日期:2000-01-01 00:00:00
abstract::Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethor...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00030.2018
更新日期:2020-01-01 00:00:00
abstract::The Arp2/3 complex is an evolutionary conserved molecular machine that generates branched actin networks. When activated, the Arp2/3 complex contributes the actin branched junction and thus cross-links the polymerizing actin filaments in a network that exerts a pushing force. The different activators initiate branched...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00006.2017
更新日期:2018-01-01 00:00:00
abstract::Traditionally the auditory system was considered a hard-wired sensory system; this view has been challenged in recent years in light of the plasticity of other sensory systems, particularly the visual and somatosensory systems. Practical experience in clinical audiology together with the use of prosthetic devices, suc...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00002.2002
更新日期:2002-07-01 00:00:00
abstract::Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded prot...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00001.2011
更新日期:2011-10-01 00:00:00
abstract::It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells are ideally positioned to respond to hormones, which act in concert with locally produced chemical mediators to regulate their growth, motility, functio...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00024.2009
更新日期:2009-10-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MA...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.143
更新日期:1999-01-01 00:00:00
abstract::This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on rea...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1996.76.3.839
更新日期:1996-07-01 00:00:00
abstract::The pancreatic β-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasm...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00009.2016
更新日期:2016-10-01 00:00:00
abstract::Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body m...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00016.2008
更新日期:2009-04-01 00:00:00
abstract::Molecular research on ion channels has demonstrated that many of these integral membrane proteins associate with partner proteins, often versatile in their function, or even assemble into stable macromolecular complexes that ensure specificity and proper rate of the channel-mediated signal transduction. Calcium-activa...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00049.2009
更新日期:2010-10-01 00:00:00
abstract::Voltage-sensing phosphatase (VSP) contains a voltage sensor domain (VSD) similar to that in voltage-gated ion channels, and a phosphoinositide phosphatase region similar to phosphatase and tensin homolog deleted on chromosome 10 (PTEN). The VSP gene is conserved from unicellular organisms to higher vertebrates. Membra...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00056.2017
更新日期:2018-10-01 00:00:00
abstract::During the last decade, earlier suggestions that insulin acts at the plasma membrane level via combination with receptors have been amply confirmed in studies of 125I-labeled insulin binding kinetics. Efforts have been devoted to the development of homogeneous, stable, and bioactive tracers, and a preparation of monoi...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1984.64.4.1321
更新日期:1984-10-01 00:00:00
abstract::Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) comprise the 13 members of the human "C" branch of the ATP binding cassette (ABC) superfamily. All C branch proteins share conserved structural features ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00035.2005
更新日期:2006-07-01 00:00:00
abstract::This review is devoted to the molecular genetics and bioenergetics of human mitochondria related to the mechanism of aging. Morphological and functional changes of mitochondria associated with age and age-related disease are overviewed with special reference to the changes in enzymes encoded by mitochondrial-inherent ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1997.77.2.425
更新日期:1997-04-01 00:00:00
abstract::Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly co...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.3.583
更新日期:1998-07-01 00:00:00
abstract::A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This p...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1990.70.4.987
更新日期:1990-10-01 00:00:00
abstract::Glial cells respond to various electrical, mechanical, and chemical stimuli, including neurotransmitters, neuromodulators, and hormones, with an increase in intracellular Ca2+ concentration ([Ca2+]i). The increases exhibit a variety of temporal and spatial patterns. These [Ca2+]i responses result from the coordinated ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.1.99
更新日期:1998-01-01 00:00:00
abstract::Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For a long time, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochle...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00035.2019
更新日期:2020-10-01 00:00:00
abstract::Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology an...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00039.2015
更新日期:2016-07-01 00:00:00
abstract::The classic concept of gastrointestinal endocrinology is that of a few peptides released to the circulation from endocrine cells, which are interspersed among other mucosal cells in the upper gastrointestinal tract. Today more than 30 peptide hormone genes are known to be expressed throughout the digestive tract, whic...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.4.1087
更新日期:1998-10-01 00:00:00
abstract::Afferent signals that guide orienting movements converge in the deeper layers of the SC in a wide variety of animals. The sensory cells are arranged topographically according to their receptive-field locations and, thereby, form maps of sensory space. Maps of visual, somatosensory, and/or auditory space have been obta...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1986.66.1.118
更新日期:1986-01-01 00:00:00