Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 micrograms human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP provoked a transient but significant decrease in systolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial O2 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and metabolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropeptide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels.
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PMID:Plethysmographic evaluation of the vascular effects of human calcitonin gene-related peptide in man. 204 94

Calcitonin has been isolated and its structure defined from several species, including man. Synthetic preparations of several calcitonins are available for clinical use. Of these, porcine (pCT), human (hCT), and salmon (sCT) have been synthetized according to their natural sequences, while eel calcitonin (cCT) is available as amino-suberic acid derivative (ASU-eCT). The different molecular configuration results in different biological potency and tolerability. Currently, the potency of calcitonin in man is evaluated by its capacity of lowering serum calcium and stimulating cAMP plasma levels after acute infusion. In normal subjects, cAMP stimulation seems to be a more sensitive test, since plasma calcium in normal subjects is poorly affected by an acute treatment with calcitonin. On the other hand, the side effects are usually assessed by clinical observation, on the basis of duration and intensity of the symptoms. Our experience, emerging from several studies devoted to comparing the biological activity and tolerability of different calcitonin preparations in humans, indicates that the hypocalcemic effect and the increase of plasma cAMP are produced by all peptides, according to the potency order sCT greater than hCT greater than ASU-eCT. For all peptides, the most constant side effect is flushing, and the frequency order of side effects is hCT greater than sCT = ASU-eCT.
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PMID:Biological activity of different calcitonins in men. 217 71

Calcitonin gene-related peptide (CGRP) has recently been identified in central and peripheral nerve fibres, including those of blood vessels supplying the exocrine pancreas, and in pancreatic islet cells. Moreover, receptors have been characterised in the same tissue. The present study examined the effects of human CGRP and of calcitonin on exocrine pancreatic secretion and on islet cell function in nine healthy volunteers. CGRP (300 ng/kg/h) caused, respectively, a 25% and 31% inhibition of caerulein stimulated trypsin and amylase output which was similar to that seen with calcitonin (300 ng/kg/h). Arginine stimulated insulin and glucagon release was unaffected by either CGRP, or calcitonin. Calcitonin gene-related peptide caused cutaneous flushing, but did not affect the pulse rate or arterial blood pressure in the doses tested. Calcitonin gene-related peptide inhibits exocrine pancreatic secretion in vivo in man, but does not affect islet cell hormone release.
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PMID:Effect of calcitonin and calcitonin gene-related peptide on pancreatic functions in man. 327 54

Calcitonin gene-related peptide (CGRP) is a recently discovered widespread regulatory peptide which is encoded in the same gene as calcitonin. We assessed the effect of systemic infusion of synthetic rat CGRP at low dose (range 0.32-2.56 pmol/kg per min) on submaximal pentagastrin-stimulated gastric secretion and on gastrointestinal hormones. To assess its pharmacokinetic parameters in man the MCR and plasma half-life were estimated by the continuous infusion method. Gastric acid output and pepsin secretion were significantly reduced by CGRP (-29% of basal, P less than 0.01 and -40% of basal, P less than 0.005, respectively). There was a significant fall in basal levels of gastrin (-39%, P less than 0.001); gastric inhibitory peptide (-44.7%, P less than 0.001); enteroglucagon (-25%, P less than 0.001) and neurotensin (-33%, P less than 0.05). There was no significant change in plasma levels of insulin, motilin, pancreatic polypeptide or glucose. Suppression of gastric secretion and the fall in gastrointestinal hormones was prolonged and basal levels were not re-established after stopping the CGRP infusion. The disappearance curve of immunoreactive CGRP from the plasma was bi-exponential. The plasma half-life of immunoreactive CGRP was calculated as 6.9 +/- 0.9 min for the fast decay and 26.4 +/- 4.7 min for the slow decay. The calculated MCR was 11.3 +/- 1.2 ml/kg per min. Except for flushing of the face no untoward effects were observed. The results of this study suggest the possibility that CGRP could play a role in the regulation of gastric secretion and gastrointestinal hormone release.
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PMID:Infusion of a novel peptide, calcitonin gene-related peptide (CGRP) in man. Pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones. 392 13

Calcitonin gene-related peptide (CGRP) has been localized in cardiac nerve fibers and blood vessels from which it may be released as neurotransmitter or neuromodulator. Acute cardiovascular effects of i.v. administered CGRP have been studied in human subjects. CGRP (25.3 nmol) caused a mean maximal increase of the heart rate of 41 beats per min (P less than 0.01) and lowered arterial systolic and diastolic pressures by 26 mm Hg and 20 mm Hg, respectively (P less than 0.01) (n = 6 subjects). These effects were associated with facial flushing, and a rise of plasma levels of norepinephrine and epinephrine of 257 pg/ml and 9 pg/ml, respectively (P less than 0.01). Administration of equimolar amounts of human calcitonin caused no cardiovascular effects except for minor facial flushing. Serum calcium was marginally lowered with both CGRP (0.2 mg/100 ml) and calcitonin (0.4 mg/100 ml) (P less than 0.05). Furthermore, CGRP (12.7 nmol) reduced the preejection period and duration of the electromechanical systole by 26 msec and 66 msec, respectively (P less than 0.001 and P less than 0.01), presumably acting as positive inotropic agent. Labetalol, blocking adrenergic receptors, obliterated these inotropic effects, whereas the positive chronotropic and hypotensive actions of CGRP remained unchanged.
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PMID:Cardiovascular action of calcitonin gene-related peptide in humans. 393 76

Medullary cancer of the thyroid is rare but of unusual biologic interest. It originates in the thyroid parafollicular or C cells that are of neural crest origin and that secrete calcitonin. Calcitonin measurements, particularly after pentagastrim administration, are useful in detecting the tumor and following its progression. Ninety percent of medullary cancers are sporadic and 10% are familial; the latter may be associated with pheochromocytoma and parathyroid hyperplasia-adenoma. Initial symptoms of both the sporadic and familial varieties include thyroid mass, diarrhea, and less often, flushing. Uninvolved members of kindreds with the disease should be followed up by repeated measurements of calcitonin after pentagastrim and calcium infusion and should be treated when a positive test result is obtained. Therapy involves total thyroidectomy plus node dissection if indicated. In addition, postoperative radiation may reduce the recurrence rate.
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PMID:Medullary carcinoma of the thyroid. 684 63

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.
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PMID:Neuropeptides in the skin of patients with atopic dermatitis. 885 37

Calcitonin gene-related peptide (CGRP) is a very potent vasodilator in the nervous system, and may be involved in hot flushes experienced by most women around menopause. Flushing post-menopausal women had higher urinary excretion of CGRP before than after successful treatment of their flushes with acupuncture. The prevalence of vasomotor symptoms is lower in physically active women. In a rat model we therefore intended to assess whether acupuncture and exercise affected CGRP concentrations in different parts of the brain and peripherally. The aim of the study was to elucidate the short- and long-term effects of exercise and acupuncture on CGRP concentrations in the nervous system of normal adult rats. In a rat model, we examined the effects of single interventions and long-term treatment with physical exercise and manual or electro-acupuncture on CGRP concentrations in urine, cerebrospinal fluid and serum and different parts of the brain. In all compartments studied, but significantly only in the cerebrospinal fluid, CGRP increased after a single session of physical exercise or electro-acupuncture. Manual acupuncture did not change CGRP concentrations in any compartment. Rats had the highest concentrations of CGRP in the pituitary and hypothalamus but the concentrations did not differ significantly between control rats and those subjected to long-term treatment with manual or electro-acupuncture or running rats. Rats treated with electro-acupuncture had twice the CGRP concentration in the frontal cortex compared to control rats, albeit the difference did not reach statistical significance. Evidently manual and electro-acupuncture have different effects, whereas electro-acupuncture and physical exercise have more similar effects on CGRP production and/or release. To elucidate the role of CGRP in vasomotor symptoms, further studies with older flushing rats should be performed.
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PMID:Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine. 959 20

Calcitonin gene-related peptide (CGRP) concentrations are increased in postmenopausal women and castrated men with symptomatic flushing. We wanted to determine if a CGRP increase exists in the plasma of healthy fertile-age women during sweating. Plasma concentrations of CGRP were measured by radioimmunoassay at maximal sweating during a sauna session and during bicycle exercise both at maximal and 70% of maximal work capacity in 8 healthy women of fertile age. Plasma concentrations of CGRP were unaffected (>90% statistical power) during both experimental sessions. We suggest that sweating itself does not explain the rise in CGRP concentrations observed in flushing postmenopausal women.
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PMID:Calcitonin gene-related peptide during sweating in young healthy women. 1594 46