1. Binding sites for calcitonin-gene-related peptide were localized and characterized in porcine coronary arteries using quantitative autoradiography, and the density of binding sites was compared between large epicardial and small intramyocardial coronary arteries.. 2. A single class of binding sites for calcitonin-gene-related peptide with a dissociation constant of 2.1 ± 0.2 nmol/l was detected in both the large and small coronary arteries. The density of specific binding sites was higher (maximum binding site density 231 ± 14 fmol/mg of protein) in the small coronary arteries than in the large epicardial coronary arteries (maximum binding site density 108 ± 5 fmol/mg of protein). β-Human calcitonin-gene-related peptide showed higher affinity than α-human calcitonin-gene-related peptide for the binding sites. Most of the specific binding sites for both peptides in the large coronary artery were localized in the intima and media.. 3. In coronary artery from patients with coronary heart ...
article{09c0a925-e49d-4f96-88c5-8518027b9c58, abstract = {An aggregation of substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing nerve cells (internal carotid mini-ganglion) is described at the junction between the greater superficial petrosal nerve and the internal carotid nerve close to the internal carotid artery. A retrograde tracer dye technique demonstrates that this ganglion and the trigeminal and superior vagal ganglia supply the internal carotid artery with SP/CGRP fibers at, above and below this level, respectively. Implications of this finding for cranial painful syndromes in man are discussed.}, author = {Hardebo, Jan Erik and Suzuki, Norihiro and Owman, Christer}, issn = {0304-3940}, language = {eng}, number = {1}, pages = {39--45}, publisher = {Elsevier}, series = {Neuroscience Letters}, title = {Origins of substance P- and calcitonin gene-related peptide-containing nerves in the internal carotid artery of rat}, url = ...
Using a double labeling indirect immunofluorescent technique, we studied the guinea pig trigeminal ganglion and eye for co-localization of substance P and calcitonin gene-related peptide. In the trigeminal ganglion, the number of neurons immunoreactive for calcitonin gene-related peptide significantly outnumber those immunoreactive for substance P, but virtually all substance P positive neurons are immunoreactive for calcitonin gene-related peptide. In the eye, a complex pattern of co-localization is present; both peptides co-localize in most immunoreactive nerve fibers. Nerve fibers immunoreactive only for calcitonin gene-related peptide tend to be concentrated in the cornea and posterior ciliary body. Nerve fibers immunoreactive only for substance P are present in relation to both iris muscles. Sensory denervation by intracranial transection of the ophthalmic and maxillary nerves fails to eliminate these substance P positive but CGRP negative iris nerve fibers. These findings indicate an ...
article{1857c827-237f-4c9c-bdcf-df90e3a1106c, abstract = {In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. ...
TOPICAL CALCITONIN GENE-RELATED PEPTIDE INCREASES WOUND CLOSURE IN SECOND DEGREE CUTANEOUS BURNSBiologyMissouri State University, August 2012Master of ScienceDarin Thomas DieckhoffABSTRACTCutaneous thermal wounds result in significant tissue damage with loss of epidermis, nerve fibers, and vascular tissue, which increases healing time. Neuropeptides released by sensory neurons are implicated in the wound healing process. The 37-amino acid neuropeptide calcitonin gene-related peptide (CGRP) is a multifunctional protein that promotes vasodilation and proliferation of keratinocytes and endothelial cells. Based on the distribution of CGRP and its receptor in adult CD Hairless rats, we hypothesized that topical administration of CGRP to a cutaneous thermal wound would increase the rate of wound closure. Two 1.5 cm partial-thickness thermal wounds were created on the upper dorsal region of hairless rats (n = 6) by exposing tissues to 70o C water for 10 seconds. Each wound was covered with standard medical
TY - JOUR. T1 - Calcitonin gene-related peptide enhances release of native brain-derived neurotrophic factor from trigeminal ganglion neurons. AU - Buldyrev, Ilya. AU - Tanner, Nathan M.. AU - Hsieh, Hui Ya. AU - Dodd, Emily G.. AU - Nguyen, Loi T.. AU - Balkowiec, Agnieszka. PY - 2006/12/1. Y1 - 2006/12/1. N2 - Activity-dependent plasticity in nociceptive pathways has been implicated in pathomechanisms of chronic pain syndromes. Calcitonin gene-related peptide (CGRP), which is expressed by trigeminal nociceptors, has recently been identified as a key player in the mechanism of migraine headaches. Here we show that CGRP is coexpressed with brain-derived neurotrophic factor (BDNF) in a large subset of adult rat trigeminal ganglion neurons in vivo. Using ELISA in situ, we show that CGRP (1-1000 nm) potently enhances BDNF release from cultured trigeminal neurons. The effect of CGRP is dose-dependent and abolished by pretreatment with CGRP receptor antagonist, CGRP(8-37). Intriguingly, CGRP-mediated ...
Release of calcitonin gene-related peptide (CGRP) from trigeminal sensory nerves is implicated in the underlying pathology of migraine. While the therapeutic benefits of grape seed extract (GSE) to inhibit pathophysiological mechanisms associated with cardiovascular disease are well known, the potential benefit of GSE to decrease neurogenic inflammation has not been investigated. The goal of my study was to determine whether GSE could inhibit CGRP expression in primary cultures of trigeminal ganglion neurons as well as a human cell line, DMS 153 cells. CGRP was significantly increased in primary rat trigeminal ganglia cultures in response to a depolarizing stimulus by KCl or capsaicin. Pretreatment with GSE repressed stimulated release of CGRP from trigeminal ganglion neurons. Similarly, GSE repressed stimulated human CGRP promoter activity and mitogen activated protein kinases (MAPK) reporter genes in DMS 153 cells. Moreover, overnight treatment with GSE suppressed basal human CGRP promoter activity.
TY - JOUR. T1 - Calcitonin gene-related peptide in experimental ischemia. Implication of an endogenous anti-ischemic effect. AU - Gherardini, Giulio. AU - Evans, Gregory R D. AU - Theodorsson, Elvar. AU - Gurlek, Ali. AU - Milner, Stephen M.. AU - Palmer, Björn. AU - Lundeberg, Thomas. PY - 1996. Y1 - 1996. N2 - Ischemia resulting from flap harvesting and vascular manipulation during microsurgery may be responsible for flap ischemic sufferance and, ultimately, necrosis. Recently, the regulatory role of the sensory nervous system in ischemia has attracted much interest. Calcitonin gene-related peptide (CGRP), a neuropeptide, is a naturally occurring vasodilator with no constrictive effects. In the present study, we developed a model of partial, chronic ischemia in the rat epigastric flap and investigated the effects of ischemia on concentrations of CGRP-like immunoreactivity (-LI) in ischemic skin and in different regions of the rat brain (striatum, hippocampus, pituitary, hypothalamus, and ...
TY - JOUR. T1 - Engineering ex vivo-expanded marrow stromal cells to secrete calcitonin gene-related peptide using adenoviral vector. AU - Deng, Weiwen. AU - Bivalacqua, Trinity. AU - Chattergoon, Natasha N.. AU - Jeter, James R.. AU - Kadowitz, Philip J.. PY - 2004. Y1 - 2004. N2 - Calcitonin gene-related peptide (CGRP) is a target for cardiovascular gene therapy. Marrow stromal cells (MSCs) hold promise for use in adult stem cell-based cell and gene therapy. To determine the feasibility of adenoviral-mediated CGRP gene transfer into ex vivo-expanded MSCs, rat MSCs were isolated, ex vivo expanded, and transduced with adenoviruses. Adprepro-CGRP and AdntlacZ, adenoviral vectors containing prepro-CGRP or nuclear-targeted β-galactosidase reporter gene ntlacZ under the control of Rous sarcoma virus promoter, were used. In this study, it can be shown that transduction efficiency of adenoviral-mediated gene transfer into ex vivo-expanded MSCs is dose dependent, transgene expression persists for more ...
Calcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood. Synovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3-4) during total knee arthroplasty. Correlationships between the mRNA expression levels of CGRP and those of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cycloxygenase-2 (COX-2) were evaluated using real-time PCR analysis of total RNA extracted from the collected synovial tissues. To investigate the factors controlling the regulation of CGRP and CGRP receptor expression, cultured synovial cells were stimulated with TNF-α, IL-1β, IL-6, and
Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological substance on the BOLD-response per see before that substance can be used in an fMRI experiment. Furthermore MR-angiography is useful in determining the vascular site-of-action of vasoactive substances ...
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Calcitonin gene-related peptide (CGRP), a sensory neurotransmitter that is widely distributed in cardiovascular tissues, may help to counteract coronary artery vasoconstriction during anaphylaxis. CGR... more
CCA876Ra, CALCB; CGRP2; CALC2; CGRP-II; Calcitonin Gene Related Peptide 2; Calcitonin 2; Calcitonin Related Polypeptide Beta | Products for research use only!
The sensory neuropeptide calcitonin gene-related peptide (CGRP) plays a role in primary headaches and CGRP receptor antagonists are effective in migraine treatment. CGRP is a potent vasodilator raising the possibility that antagonism of its receptor could have cardiovascular effects. We therefore investigated the effects of the anti-migraine CGRP receptor antagonist telcagepant (MK-0974) on human isolated coronary arteries. Arteries with different internal diameters (ID) were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human αCGRP were greater in distal (ID: 600-1000 μm, Emax=83±7%) than proximal coronary arteries (ID: 2-3 mm, Emax=23±9%), coronary arteries from explanted hearts (ID 3-5 mm, Emax=11±3%) and coronary arterioles (ID: 200-300 μm, Emax=15±7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pre-treatment with telcagepant (10 nM to 1 ...
Muscle inflammation and hyperalgesia induced by adjuvant injection into skeletal muscle are associated with an increase in calcitonin gene-related peptide (CGRP) labeling in skeletal muscle and dorsal root ganglia (DRG). This increased expression of CGRP may contribute to the maintenance of pain in these models. However, it is not known if inflammation induced by repetitive exposure to stretch-sho
Calcitonin was discovered by C opp et al. (1961) as a hypocalcemic hormone and the neuropeptide calcitonin gene-related peptide (CGRP) recognized through analysis of the calcitonin gene structure (A...
Title:Role of CGRP-Receptor Component Protein (RCP) in CLR/RAMP Function. VOLUME: 14 ISSUE: 5. Author(s):Ian M. Dickerson. Affiliation:University of Rochester, Department of Neurobiology & Anatomy, 601 Elmwood Avenue, Box 603, Rochester, NY 14642, USA.. Keywords:Calcitonin gene-related peptide, adrenomedullin, calcitonin-like receptor, receptor activity modifying protein, CGRP-receptor component protein, signal transduction, trafficking.. Abstract:The receptor for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) requires an intracellular peripheral membrane protein named CGRP-receptor component protein (RCP) for signaling. RCP is required for CGRP and AM receptor signaling, and it has recently been discovered that RCP enables signaling by binding directly to the receptor. RCP is present in most immortalized cell lines, but in vivo RCP expression is limited to specific subsets of cells, usually co-localizing with CGRP-containing neurons. RCP protein expression correlates with CGRP ...
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Migraine is among the most common types of pain, but its mechanisms are poorly understood. A growing body of evidence points to a critical role of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine headache. During migraine, CGRP is thought to be released from peripheral endings of perivascular meningeal nociceptors primary and to promote vasodilatation. A current hypothesis suggests that peripheral CGRP and its related meningeal vasodilatation results in activation and sensitization, leading to the generation of migraine headache. However, direct evidence supporting this idea is lacking. Here, using electrophysiological, extracellular, single-unit recording combined with laser-Doppler flowmetry measurements of dural blood flow (DBF), we examined whether CGRP and meningeal vasodilatation promote activation or sensitization of meningeal nociceptors. Changes in (DBF), ongoing discharge, and responsiveness to mechanical stimulation of the dura were studied after either ...
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Understanding of the neuropathology leading to migraine pain has centered on either a vascular or neuronal origin. Sildenafil, a specific inhibitor of phosphodiesterase 5 (PDE5), induces migraine-like headache in a human headache model without concomitant artery dilation. The presence and activity of PDE3 and PDE5 is known in cerebral arteries. However, the presence in the neuronal part of the trigeminovascular pathway, i.e. the trigeminal ganglion and the possible co-localization with calcitonin gene-related peptide (CGRP), is not known ...
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In cultured chicken myotubes, calcitonin gene-related peptide (CGRP), a peptide present in spinal cord motoneurons, increased by 1.5-fold the number of surface acetylcholine receptors (AChRs) and by threefold AChR alpha-subunit mRNA level without affecting the level of muscular alpha-actin mRNA. Cholera toxin (CT), an activator of adenylate cyclase, produced a similar effect, which did not add up with that of CGRP. In contrast, tetrodotoxin, a blocker of voltage-sensitive Na+ channels, elevated the level of AChR alpha-subunit mRNA on top of the increase caused by either CGRP or CT. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C, markedly decreased the cell surface and total content of [125I]alpha BGT-binding sites and reduced the rate of appearance of AChR at the surface of the myotubes without reducing the level of AChR alpha-subunit mRNA. Moreover, TPA inhibited the increase of AChR alpha-subunit mRNA caused by tetrodotoxin without affecting that produced by CGRP ...
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We previously found that capsaicin can dilate third-order arterioles in striated muscle by a mechanism that appears to involve release of endogenous calcitonin gene-related peptide (CGRP). Experiments were done to determine 1) whether capsaicin has similar effects on larger arterioles and venules and 2) whether relaxation involves endogenous CGRP and synthesis of endothelium-derived relaxing factor. In male Sprague-Dawley rats anesthetized with pentobarbital (50 mg/kg, i.p.), we examined responses of first- and second-order microvessels in the cremaster muscle using video microscopy. Addition of capsaicin (0.1 microgram/ml) to vessels constricted by norepinephrine (10(-7) M) dilated 1As by 91% +/- 28%, 2As by 113% +/- 18% 1Vs by 11% +/- 6% and 2Vs by 42% +/- 18%. Capsaicin in the presence of the specific CGRP receptor antagonist CGRP (8-37) caused an attenuated arteriolar dilation but had no significant venodilatory effect (1As 29% +/- 18%, 2As 55% +/- 14%, 1Vs 7% +/- 3%, 2Vs 16% +/- ...
Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats with experimental diabetes; effects of insulin and aldose reductase ...
Calcitonin gene related peptide (CGRP), a 37 amino acid neuropeptide, is the most potent vasodilator known. Participation of CGRP in hypertension and related diseases, such as preeclampsia or vasospasm after subarachnoid haemorrage, is one of the most studied topics. In this review we summarize the published roles of CGRP in pathophysiology of hypertension in humans and in experimental models. We also discuss the effects of direct administration of CGRP in the treatment of hypertension and of anti-hypertensive drugs that enhance the release or response of endogenous calcitonin gene-related peptide: angiotensin converting enzyme inhibitors, selective antagonists for the angiotensin II receptor, beta-blockers, magnesium sulphate for preeclampsia and rutaecarpine, as well as the possibilities using CGRP in gene therapy for prevention of vasospasm after subarachnoid haemorrage ...
Our laboratory studies the neuropeptide calcitonin gene-related peptide (CGRP). Originally discovered as an alternatively-spliced variant of the calcitonin mRNA, CGRP is one of the most potent vasodilators known. As a vasodilator, CGRP has both peripheral and central effects. One of the most notable effects of CGRP is its causative effect of migraine on the cerebral vasculature, and stable synthetic antagonists have been recently developed and are in Stage III clinical trials for migraine treatment. CGRP also suppresses immune function, is involved in pain perception, and has further central role in the development of tolerance to opiates ...
After a long illness borne with much grace and dignity, Iain MacIntyre died in London on 18 September 2008. He had led a most distinguished career over five decades as a major figure in the field of calcium-regulating hormones and bone metabolism, with his many scientific achievements marked by originality as well as biological and medical importance. Among his many accomplishments were the co-discovery with Harold Copp of the hormone calcitonin, whose glandular origin, structure and biological and medical functions he defined. Iain also was the first to isolate and sequence, with colleagues, the novel human neuropeptide calcitonin gene-related peptide, demonstrating its role as a potent vasodilator. Subsequently Iain defined the multiple phenotypic consequences attributable to nitric oxide production by different enzymes in a tissue-specific fashion. A major educational contribution was in conceiving and organizing an important biennial series of international endocrine meetings held between ...
J Med Chem. 2008 Aug 28;51(16):4858-61. Epub 2008 Jul 30.Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure. To Reference ...
Background: Calcitonin gene-related peptide (CGRP) is a neuropeptide with broad salutary cardiovascular effects. Mechanisms underlying cardiac CGRP regulation are poorly understood. The intrinsic cardiac adrenergic (ICA) cell is a novel cardiac neuroendocrine cell that expresses the δ-opioid receptor. We have shown that δ-opioid stimulation of ICA cells induces epinephrine liberation exerting an infarct-size limiting effect via β2-adrenoreceptor (β2-AR) stimulation. In this study we hypothesize that ICA cells synthesize and release CGRP which is involved in myocardial function and that CGRP gene expression can be autoregulated by epinephrine released from the ICA cell or regulated exogenously via β2-AR agonist.. Methods and Results: In situ hybridization coupled with immunofluorescent double labeling localized CGRP mRNA expression exclusively to ICA cells in explanted human left ventricular tissue. To determine whether δ-opioid-enhanced epinephrine release from ICA cells autoregulates CGRP ...
Abstract We have compared the density of nerve fibres in the synovium in club foot with that of specimens obtained from the synovium of the hip at operations for developmental dysplasia. The study focused on the sensory neuropeptides substance P; calcitonin gene-related peptide; protein gene product 9.5, a general marker for mature peripheral nerve fibres; and growth associated protein 43, a neuronal marker for new or regenerating nerve fibres. In order to establish whether there might be any inherent difference we analysed the density of calcitonin gene-related peptide-positive nerve fibres in the hip and ankle joints in young rats. Semi-quantitative analysis showed a significant reduction in the number of sensory and mature nerve fibres in the synovium in club foot compared with the control hips. Calcitonin gene-related peptide (CGRP) positive fibres were reduced by 28%, substance P-positive fibres by 36% and protein gene product 9.5-positive fibres by 52% in club foot. The growth associated protein
Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were ...
Schuler, B; Rieger, G; Gubser, M; Arras, M; Gianella, M; Vogel, O; Jirkof, P; Cesarovic, N; Klohs, J; Jakob, P; Brock, M; Gorr, T A; Baum, O; Hoppeler, H; Samillan-Soto, V; Gassmann, M; Fischer, J A; Born, W; Vogel, J (2014). Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice. Acta Physiologica, 211(1):107-121.. Hlushchuk, R; Ehrbar, M; Reichmuth, P; Heinimann, N; Styp-Rekowska, B; Escher, R; Baum, O; Lienemann, P; Makanya, A; Keshet, E; Djonov, V (2011). Decrease in VEGF expression induces intussusceptive vascular pruning. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(12):2836-2844.. Richter, V; Savery, M D; Gassmann, M; Baum, O; Damiano, E; Pries, A R (2011). Excessive erythrocytosis compromises the blood-endothelium interface in erythropoietin-overexpressing mice. Journal of Physiology, 589(21):5181-5192.. Picard, N; Baum, O; Vogetseder, A; Kaissling, B; Le Hir, M (2008). Origin of renal myofibroblasts in the model of ...
The goals of this study were to evaluate the influence of CGRP within the BNST on anxiety and on neural activation patterns. We found that intra-BNST CGRP infusions produced an anxiogenic behavioral profile and enhanced neural activation in a number of anxiety-related brain areas, and that antagonism of these receptors prevented anxiety-like responses to TMT odor. CGRP infused bilaterally into the BNST enhanced the acoustic startle response in a dose-dependent manner (experiment 1). This increase was attenuated by prior administration of the CGRP antagonist, αCGRP8-37, at a dose that did not significantly affect startle when given alone (experiment 2). This suggests that the effects on startle were indeed mediated by activation of CGRP receptors. Intra-BNST CGRP infusions (800 ng/side) also decreased the percentage of time spent on the open arms and the percentage of total entries into the open arms of the elevated plus maze (experiment 6). These anxiety-like behavioral results are consistent ...
Background and purpose: Long-term morphine treatment enhances pain neurotransmitter (such as calcitonin gene-related peptide (CGRP)) levels in the spinal cord. It has been suggested previously that increased spinal CGRP may contribute to sustained morphine-mediated paradoxical pain sensitization and antinociceptive tolerance. Previous in vitro studies from our group indicated that Raf-1 kinase-mediated adenylyl cyclase superactivation played a crucial role in sustained morphine-mediated augmentation of basal and evoked CGRP release from cultured primary sensory neurons. The present study was aimed to evaluate the physiological significance of this molecular mechanism in vivo, in rats ...
The present study demonstrated for the first time that neonatal degeneration of capsaicin-sensitive sensory nerves in rats leads to a significant increase in blood pressure when a high sodium diet is given. This observation is important because it has been shown that (1) substantial decreases in CGRP-containing sensory nerves in the mesenteric arterial bed occur in spontaneously hypertensive rats (SHR),6 7 indicating that there are inherited abnormalities in either generation or maintenance of sensory nerves in SHR; (2) the plasma CGRP concentration is lower in adult SHR than in age-matched normotensive control rats, indicating that release of CGRP from sensory nerves is decreased in SHR21 ; and (3) vasodilator responses to exogenous CGRP increase with age in SHR, suggesting that sensitivity of receptors to CGRP is increased due to the decreased release of CGRP from sensory nerves.6 7 The defect in sensory vasodilator function may produce an imbalance that could contribute to the development and ...
in Journal of Pharmacology and Experimental Therapeutics (The) (1994), 270(1), 30-6. The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the ... [more ▼]. The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the arterial, capillary and venous pressures and the capillary filtration coefficient (Kf,c). CGRP was administered alone or in combination with capsaicin (10(-4) M), acetylcholine (ACh) (10(-11) M to 10(-7) M), substance P (SP) (10(-10) M to 10(-6) M) and serotonin (10(-4) M). The influence of a specific antagonist of CGRP receptors, CGRP8-37 (10(-8) M), on the pulmonary edema induced by these mediators was also considered. CGRP had no direct effect on the vascular pressures or on Kf,c. Capsaicin and ...
Die bakterielle Meningitis (BM) ist trotz antibiotischer Therapie eine Erkrankung mit einer hohen Mortalität und Morbidität. Kopfschmerzen und Meningismus sind Hauptsymtome und ein klinischer Hinweis für die Aktivierung trigeminaler Fasern. Ziel dieser Arbeit war es zu prüfen ob die freigesetzten Neuropeptide einen proinflammatorischen Effekt auf zerebrale Endothelzellen, einen wesentlichem Bestandteil der Blut-Hirn-Schranke haben. Wir verwendeten primär kultivierte zerebrale Kapillarendothelzellen (BMEC) der Ratte und als Stimulus Neuropeptide und/oder Pneumokokkenzellwände (PCW). Beide Neuropeptide, CGRP mehr als SP, verstärken den Effekt von PCW auf die mRNA Expression und Freisetzung von TNF-alpha, IL-1beta, IL-6, IL-10 und MIP-2 aus den BMEC. CGRP und SP haben nur eine geringe Wirkung. PCW regulieren die Dichte der CRLR (CGRP1-R) bzw. NK-1 Rezeptoren und erklären damit die kostimulatorische Wirkung. Zudem untersuchten wir den Effekt von PCW und/oder CGRP auf die Adrenomedullin (AM)- ...
This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism. Calcitonin gene-related peptide functions as a vasodilator while katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have been found for this gene ...
Maintenance of the gastric mucosal barrier is important in terms of protection from harmful substances such as hydrogen ions that are secreted from the mucosa and are capable of producing cell injury.38 Little is known of whether or not gastric neurones contribute towards gastric mucosal protection from injury, although the vagus nerve has long been regarded as a permissive factor in peptic ulcer disease. Recently, extrinsic afferent neurones were found to operate as a neural emergency system in the digestive tract.1 Released neuropeptides from their peripheral endings are known to regulate a variety of physiological functions, including an increase in resistance of the tissue to injury and enhancement of repair of damaged tissues. To study the roles of these sensory neurones, capsaicin, which can act on certain primary afferent neurones and can release neuropeptides selectively, is widely used.39. The pathophysiological involvement of prostaglandins in the nervous systems, including the ...
|p|AQP1 is a polypeptide hormone produced in pancreatic beta-cells that belongs to the family of calcitonin gene-related peptides. There is a 20% sequence homology between AQP1 and calcitonin and 44% homology with calcitonin gene-related peptide. AQP1 and its fragments stimulate the proliferation of osteoblasts, inhibit bone resorption, and increase bone density and the amount of bone mass.Analysis of the deduced amino acid sequence suggested that CHIP28 protein contains 6 bilayer-spanning domains, 2 exofacial potential N-glycosylation sites, and intracellular N and C termini. The sequence showed strong homology with the major intrinsic protein of bovine lens (MIP26), which is the prototype of an ancient family of membrane channels.|/p|
New medicines are now on the market that contain antibodies against CGRP and bind to the receptor that the CGRP binds to. They are called monoclonal antibodies (MABs) and are large molecules that do not cross the blood-brain barrier and they are not digested by the liver, which prevents liver toxicity or interactions with other drugs and gives them a longer half-life than many chemical drugs, but must be given parenterally (preferably by injection) to be absorbed properly by the body. They have been proved to be effective in migraine patients both with and without aura, and both episodic and chronic migraineurs. These are the first class of preventive medications originally designed and approved for migraineurs.[25] Monoclonal means all the antibodies are made from the same genetic material, although different MABs may derive from different sources, e.g. from hamster ovarian cells, from yeast cell or from humanized cell cultures. The antibodies are also made repeatedly to make them all ...
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ラット腰椎後縦靭帯における侵害受容神経と交感神経の関わりーCalcitonin gene-related peptide とtyrosine hydroxylase の免疫組織化学と免疫電顕による考察ー ...
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The neurotransmitter calcitonin gene-related peptide (CGRP) is enriched in the adult rat trigeminal visceral projection to the cerebral arteries compared both to other neurotransmitters in this projection and to the percentage of CGRP-positive trigeminal cells projecting to cutaneous targets. In colchicine-treated ganglia approximately 30% of adult trigeminal ganglion cells projecting to the middle cerebral artery contain CGRP. Several possible developmental mechanisms underlying this enrichment were investigated. Some of this enrichment is accounted for by a prenatal selection of CGRP cells in the cerebrovascular projection. The remainder of the enrichment can be explained by a late (postnatal days 55--90)target-induced expression of CGRP in some trigeminal neurons innervating cerebral arteries. Most surprisingly, the massive postnatal regression in the trigeminal projection to the cerebral arteries (between postnatal days 5 and 55, cell death and axon retraction delete 3/4 of the neurons that ...
Dear sir: I am urgently need human beta calcitonin gene related peptide gene for my method. Please tell me where to get or buy the gene. Thanks Sincerely Huaichun Wang Institute of Medical Information 27 Taiping Road Beijing 100850 China Fax: 8610 8213044 ...
Throughout my academic career, I have been focusing on the regulation of vascular tone in health and disease (diabetes type I and II, stroke, hypertension, congestive Heart Failure and age-related changes).. Coronary arteries are densely innervated by sensory nerve endings containing calcitonin gene-related peptide (CGRP). CGRP is a potent naturally occuring 37 amino acid vasodilatory neuropeptide which is released from the perivascular sensory nerve endings in the wall of flow regulating intramural coronary arteries during hypoxia and by low pH levels in the myocardium, thus suggesting a vasodilatory role under ischemic conditions.. Receptor subtypes for CGRP, the intracellular signalling pathways and the mechanism behind CGRP-induced desensitization are still under investigation in both resistance and conductance arteries of different species including human. So far, these studies clearly demonstrate a larger CGRP receptor density in resistance arteries (internal lumen diameter < 200 µm) ...