Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Sensory nerves are important for the initiation of neurogenic inflammation and tissue repair. Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been implicated in neurogenic vasodilatation and inflammatory responses. 2. A blister model in the rat hind footpad was used as a site to induce neurogenic vasodilatation in response to antidromic electrical stimulation of the sciatic nerve. Blood flux was monitored with a laser Doppler flow monitor. 3. The quantitative contributions of CGRP and NO to vasodilatation were examined by use of the CGRP receptor antagonist CGRP8-37 and NO synthase inhibitors 7-nitroindazole (7-NI), 3-bromo 7-NI and N(G)-nitro L-arginine methyl ester (L-NAME). The potential modulatory role of endothelin was examined by use of the ET(A) receptor antagonist BQ-123. 4. CGRP8-37 (10 microM) was perfused over the blister base before nerve stimulation and continuously throughout the post-stimulation period, resulting in a significant reduction (41%) in the blood flux vascular response. 5. Pretreatment with the specific neuronal NO synthase inhibitors, 7-NI and 3-bromo 7-NI (10 mg kg(-1), i.v.), and of the non-specific L-NAME (100 microM), resulted in significant inhibition of the blood flux response (36%, 72% and 57% decrease, respectively). In contrast, 7-NI treatment in young rats pretreated with capsaicin had no further effect on the vascular response, suggesting that the source of NO is the sensory nerves. 6. BQ-123 (10 microM) significantly enhanced the stimulation-induced blood flux response (61% increase). When 7-NI was co-administered with either CGRP8-37 or BQ-123, the drug actions were additive, suggesting that there was no interaction between NO and CGRP or endothelin. 7. These data suggest that both NO and CGRP participate in neurogenic vasodilatation in rat skin microvasculature and that this response is modulated by endogenous endothelin.
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PMID:CGRP and nitric oxide of neuronal origin and their involvement in neurogenic vasodilatation in rat skin microvasculature. 953 14

The mechanism of prostaglandin E2-, prostaglandin F2alpha- and latanoprost acid (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha)-induced relaxation of the rabbit submental vein was studied. Prostaglandin E2 caused maximum relaxation of endothelin-1 precontracted vessels (EC50: 1.8 x 10(-8) M). Much of the relaxation could be abolished by denuding the endothelium with the nitric oxide synthase inhibitor, L-NAME (N(G)-Nitro-L-arginine methylester). CGRP-(8-37) (calcitonin gene-related peptide fragment (8-37)), a calcitonin gene-related peptide receptor antagonist, exhibited a partial blocking effect, whereas the tachykinin NK1 receptor blocker, GR 82334 ([D-Pro9[Spiro-gamma-Lactam]Leu10,Trp11]physalaemin (1-11)), markedly attenuated the response. Both prostaglandin F2alpha and the relatively selective FP receptor agonist, latanoprost acid, caused relaxation of the veins to about 50% of the precontracted state in the presence of GR 32191B ([1R-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-he ptenoic acid), a thromboxane receptor antagonist (EC50: for prostaglandin F2alpha 7.9 x 10(-9) M, and for latanoprost acid 4.9 x 10(-9) M). L-NAME, as well as denuding the endothelium, completely abolished the effect. In addition, most or at least a large part of the relaxation was also blocked by CGRP-(8-37) as well as GR 82334. These results indicate that the FP receptor-mediated relaxation of veins is based on release of nitric oxide in addition to involvement of calcitonin gene-related peptide and substance P, or some other tachykinin, probably released from perivascular sensory nerves. The more pronounced relaxation induced by prostaglandin E2 could be due to vasodilator EP receptors in the smooth muscle layer of the veins.
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PMID:Mechanism of prostaglandin E2-, F2alpha- and latanoprost acid-induced relaxation of submental veins. 953 15

A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, NG-nitro-L-arginine methyl ester (L-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. L-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.
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PMID:Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats. 957 25

The effects of human adrenomedullin-(13-52) [hADM-(13-52)] were investigated in the rat pulmonary vascular bed and in isolated rings from the rat pulmonary artery (PA). Under conditions of controlled blood flow and constant left atrial pressure when tone was increased with U-46619, injection of hADM-(13-52) produced dose-related decreases in lobar arterial pressure. Pulmonary vasodilator responses in the intact rat and vasorelaxant responses to hADM-(13-52) in rat PA rings were inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and L-N5-(1-iminoethyl)-ornithine hydrochloride (L-NIO). Vasorelaxant responses to hADM-(13-52) were also inhibited by methylene blue, endothelium removal, hADM-(26-52), and iberiotoxin, whereas meclofenamate, calcitonin gene-related peptide-(8-37) [CGRP-(8-37)], glibenclamide, and apamin were without effect. Because vasorelaxant responses to NS-1619, a large-conductance Ca(2+)-activated K+ channel agonist, were not altered by L-NAME and vasorelaxant responses to acetylcholine and CGRP were not altered by hADM-(26-52), the present data suggest that ADM-(13-52) acts on a receptor in the pulmonary vascular bed that is coupled to endothelial nitric oxide release. These data suggest that this nitric oxide release may lead to guanosine 3',5'-cyclic monophosphate-dependent K+ channel activation, which produces a pulmonary vasorelaxant response through hyperpolarization of vascular smooth muscle cells. The present data suggest that ADM-(13-52) modulates receptor-mediated, but not voltage-dependent, pulmonary vascular contraction by influencing Ca2+ influx. These results suggest that the ADM fragment, hADM-(13-52), acts as an endothelium-dependent vasodilator agent in the pulmonary vascular bed of the rat.
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PMID:Analysis of responses to adrenomedullin-(13-52) in the pulmonary vascular bed of rats. 957 29

To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.
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PMID:Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue. 960 32

Endomorphin 1 and 2, newly discovered endogenous ligands for the mu-opioid receptor, have vasodepressor activity in the rat. In the present study, the mechanism mediating hemodynamic responses to endomorphin 2 and the endomorphin analog [D-Ala2]endomorphin 2 (TAPP) was investigated in the rat. Intravenous injections of TAPP and endomorphin 2 produced similar dose-dependent decreases in systemic arterial pressure and were approximately 10-fold more potent than Met-enkephalin. TAPP and endomorphin 2 decreased heart rate, cardiac output, and total peripheral resistance. Under constant-flow conditions, injections of TAPP and endomorphin 2 into the perfusion circuit produced decreases in hindquarter perfusion pressure, and vasodilator responses were attenuated by the opioid receptor antagonist naloxone. Hindquarter vasodilator responses to TAPP and endomorphin 2 were attenuated by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg iv), whereas responses to the endothelium-independent vasodilators calcitonin gene-related peptide, diethylamine/nitric oxide, and isoproterenol were not changed. Hindquarter vasodilator responses to TAPP and endomorphin 2 were not altered by the cyclooxygenase inhibitor sodium meclofenamate, the ATP-dependent K+ channel antagonist U-37883A, or the presence of a time-delay coil in the perfusion circuit. These results indicate that vasodilator responses to TAPP and endomorphin 2 are mediated by the activation of a naloxone-sensitive opioid receptor and the release of nitric oxide from the endothelium within the hindquarter vascular bed of the rat.
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PMID:D-[Ala2]endomorphin 2 and endomorphin 2 have nitric oxide-dependent vasodilator activity in rats. 961 81

Nitric oxide (NO) is a novel neurotransmitter candidate to which a large number of physiological roles has been ascribed. In the present study, immunocytochemistry was used to demonstrate NO synthase (NOS) and to investigate possible co-localization with other neurotransmitters. In the trigeminal ganglion of the cat, a moderate number of NOS immunoreactive nerve cell bodies was seen, of which the major part also expressed calcitonin gene-related peptide (CGRP). The nerve cell bodies expressing NOS in the trigeminal ganglion were predominantly of small to medium size; while numerous cell bodies of varying size contained CGRP. With in situ hybridization using oligonucleotide probes, CGRP mRNA was demonstrated in almost all trigeminal neurons of the cat. Stimulation of the nasociliary nerve resulted in a frequency-dependent increase in ipsilateral local cortical blood flow by 30 +/- 6%. Administration of the NOS inhibitor NG-nitro-L-arginine-methylester (L-NAME) did not significantly alter this response when applied intravenously or on the cortical surface. Local cortical administration of the CGRP blocker h-CGRP (8-37) did not alter the cerebral vasodilator response to hypercapnia or resting flow. However, the nasociliary nerve response was reduced by 50% after h-CGRP (8-37), with a general shift to the right of the frequency-response curve. These data suggest that although NOS is seen in several trigeminal ganglion cells and coexists with CGRP in a subpopulation of the sensory neurons, its role in trigeminally mediated vasodilatation was not significant.
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PMID:Calcitonin gene-related peptide and nitric oxide in the trigeminal ganglion: cerebral vasodilatation from trigeminal nerve stimulation involves mainly calcitonin gene-related peptide. 968 99

The aim of the study was to evaluate both morphologically and functionally the distal large intestine from the aganglionic lethal spotted (ls/ls) mutant mouse and their healthy litter mates. Immunohistochemically, the aganglionic murine distal large intestine showed an absence of nerve cell bodies, and a reduction or absence of nerve fibers displaying immunoreactivity (IR) for protein gene product (PGP), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), galanin and calcitonin gene-related peptide (CGRP), while in the ganglionic large intestine these neuronal populations were abundantly present throughout the gut wall. Pathological nerve trunks within the afflicted intestinal segment were found to harbour PGP- and neuropeptide Y (NPY)-IR nerve fibers. Smooth muscle specimens from the distal part of the murine distal large intestine were mounted as ring preparations in vitro and subjected to electrical field stimulation (EFS). EFS (4-20 Hz) caused a contraction in both ganglionic and aganglionic intestine. After pretreatment with atropine EFS (20 Hz) evoked a biphasic motor response, a relaxation followed by a contraction in control specimens, while no motor response was seen in aganglionic intestine. Addition of the NOS-inhibitor N-nitro-L-arginine methyl ester (L-NAME) caused per se a weak and transient contraction and reduced the amplitude of the EFS-induced relaxation in control intestine.
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PMID:Functional and morphological examination of ganglionic and aganglionic distal gut from the lethal spotted mouse. 978 48

Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and NG-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.
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PMID:Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats. 981 36

Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP1 receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40-72% and rat alpha-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP1 receptor antagonist CGRP-(8-37) (9.6-19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal alpha-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) prevented AM protective action. L-Arginine but not D-arginine blocked L-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.
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PMID:Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats. 984 51


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