UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A possible role of nitric oxide (NO) as a modulator of capsaicin-sensitive sensory neurotransmission in blood vessels was investigated in the rat isolated mesenteric arterial bed. 2. Electrical field stimulation (EFS) of methoxamine-preconstricted mesenteric beds elicited frequency-dependent vasorelaxation mediated by capsaicin-sensitive sensory nerves. N(G)-nitro-L-arginine methyl ester (L-NAME, 10 and 300 microM) and 7-nitroindazole (7-NI, 100 microM), inhibitors of nitric oxide synthase (NOS), augmented sensory neurogenic vasorelaxation. D-NAME (300 microM), 6-aminoindazole (100 microM) and N(omega)-propyl-L-arginine (50 nM), a selective inhibitor of neuronal NOS, were without effect. The effect of 10 microM L-NAME was reversed by L-arginine (1 mM), the substrate for NOS. 3. L-NAME (300 microM) and 7-NI (100 microM) had no significant effect on vasorelaxations to calcitonin gene-related peptide (CGRP), the principal motor neurotransmitter of capsaicin-sensitive sensory nerves in rat mesenteric arteries, or to capsaicin, indicating a prejunctional action. The inhibitors of NOS had no effect on vasorelaxation to forskolin, but augmented vasorelaxation to sodium nitroprusside (SNP). 4. Removal of the endothelium augmented sensory neurogenic vasorelaxation, but did not affect vasorelaxation to CGRP, indicating a prejunctional action of endothelial NO. 5. In the absence of endothelium, L-NAME (300 microM) inhibited, and 7-NI (100 microM) caused no further augmentation of sensory neurotransmission. 6. SNP (100 nM), a nitric oxide donor, attenuated sensory neurogenic relaxations to EFS. 7. In rat isolated thoracic aortic rings, L-NAME (100 microM) and 7-NI (100 microM) attenuated concentration-dependent relaxations to acetylcholine. 8. These data show that NO modulates sensory neurotransmission evoked by EFS of the rat isolated mesenteric arterial bed, and that when NO synthesis is blocked sensory neurogenic relaxation is augmented. The source of NO is the vascular endothelium.
...
PMID:Endothelial nitric oxide modulates perivascular sensory neurotransmission in the rat isolated mesenteric arterial bed. 1218 27

The capsicum alkaloid capsaicin is an afferent fibre exciter. In the vesical bladder, capsaicin acts by releasing peptides stored in afferent fibres. The aim of this work was to verify the activity of capsaicin on in-vitro lamb urinary bladder and to ascertain whether this alkaloid evokes peptide release. Capsaicin relaxed about 80% of the lamb detrusor muscle preparations tested and contracted about 20%. Whereas neurokinin A and substance P antagonists, administered alone or together, left the contractile responses to capsaicin unchanged, atropine and tetrodotoxin totally inhibited contraction. Ruthenium red and indometacin abolished contractions and relaxation. The substance P and neurokinin A antagonists and the NO-synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) left relaxation unchanged; conversely, the calcitonin gene-related peptide antagonist alpha h-CGRP (8-37) abolished this response. These results suggest that capsaicin relaxes lamb detrusor muscle not through tachykinins but by releasing CGRP from afferent fibres. Our observation that indometacin blocks the capsaicin response in in-vitro lamb urinary bladder also suggests a role of prostanoids.
...
PMID:Tachykinin-independent activity of capsaicin on in-vitro lamb detrusor. 1219 26

We studied the mechanism of calcitonin gene-related peptide (CGRP)-induced vasorelaxation in isolated uterine vascular beds of pregnant rats. The vascular beds were perfused in situ with Krebs buffer containing dextran and indomethacin, an inhibitor of cyclooxygenase. Baseline perfusion pressure was maintained with norepinephrine. When applied as a bolus, CGRP caused a decreased perfusion pressure in uterine vascular beds that was dose-dependent and equal in both mid-pregnant and late-pregnant rats. The non-selective inhibitor of nitric oxide synthase (NOS), Nomega-nitro-L-arginine methyl ester (L-NAME), did not significantly affect CGRP-induced vasodilatation in vascular beds of either group. CGRP-induced vasodilatation was not influenced by preincubation with the inhibitors of adenylate cyclase (SQ 22536 or MDL 12330A), but was significantly attenuated by the selective inhibitor of soluble guanylate cyclase (ODQ). The vasorelaxant effect of CGRP was not significantly influenced by the inhibitor of voltage-gated potassium (KV) channels (4-aminopyridin), but was significantly attenuated by an inhibitor of calcium-regulated potassium (KCa) channels (tetraethylammonium) and by an inhibitor of adenosine triphosphate-sensitive potassium (KATP) channels (glibenclamide). The gap junction uncoupling agent (carbenoxolone) also significantly attenuated the CGRP-induced decrease in perfusion pressure. We conclude that vasorelaxation induced by CGRP in the pregnant rat uterine vascular bed is not dependent on endothelial nitric oxide. In the uterine circulation of late-pregnant rats, the CGRP effect involves activation of soluble guanylate cyclase, but not adenylate cyclase, and does involve KCa and KATP channels and gap junctions.
...
PMID:Calcitonin gene-related peptide dilates the pregnant rat uterine vascular bed via guanylate cyclase, ATP- and Ca-sensitive potassium channels and gap junctions. 1256 57

Adrenomedullin (AM) is a vasoactive hormone which exerts its action through cyclic adenosine monophosphate(cAMP) /cAMP-dependent protein kinase (PKA) cascade and intracellular Ca2+ mobilization. Recently, evidence has accumulated that AM plays a critical role in the regulation of vascular tone, remodeling and morphogenesis. And although numerous reports have examined the action of AM on cultured vascular cells, the results have not been consistent and have depended on the experimental conditions used. Accordingly, the purpose of this study was to clarify the effect of AM on the proliferation and migration of cultured endothelial cells. Our results revealed that AM promoted the growth and migration of endothelial cells (ECs). AM significantly promoted the proliferation of human umbilical vein endothelial cells (HUVECs) (56.0 +/- 8.7% over the controls at 10(-9) mol/l) and this stimulative effect was inhibited by two AM antagonists, AM(22-52) and calcitonin gene-related peptide (CGRP) (8-37). The number of HUVECs migrated to the lower surface of the transwell apparatus was also increased dose-dependently in the AM group (30.4 +/- 4.2% over the controls at 10(-7) mol/l), and this increase was suppressed by the two AM antagonists and by two PKA antagonists, adenosine 3'5'-cyclic monophosphorothioate Rp-isomer and myristoylated protein kinase A inhibitor amide 14-22. The promoting action of AM on endothelial migration was also suppressed by LY294002, an inhibitor for phosphatidylinositol 3-kinase, but not by N(G)-nitro-L-arginine-methyl ester (L-NAME), an antagonist for nitric oxide synthase (NOS). These results indicate that AM promotes proliferation and migration of ECs via a cAMP/PKA dependent pathway and lend support to the idea that AM exerts beneficial effects on vascular regeneration and might be used as a novel therapeutic strategy for patients with vascular disease.
...
PMID:Adrenomedullin promotes proliferation and migration of cultured endothelial cells. 1263 Aug 17

Activation of colonic proteinase-activated receptor-2 (PAR-2) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is under debate and could be neurogenic and/or the consequence of tight-junction opening with passage of exogenous pathogens into the lamina propria. The present study aimed to further characterize the inflammatory effect of PAR-2 activation by investigating: 1) the role of NO, 2) the role of afferent neurons, and 3) a possible cause and effect relationship between colonic paracellular permeability changes and mucosal inflammation. Thus, intracolonic infusion to mice of the PAR-2-activating peptide, SLIGRL, increased both myeloperoxidase (MPO) activity and damage scores indicating colonic inflammation, and enhanced colonic permeability to (51)Cr-EDTA from 2 to 4 h after its infusion. NO synthase inhibitors, L-NAME and aminoguanidine, as well as the neurotoxin capsaicin and NK1, calcitonin gene-related peptide (CGRP) receptor antagonists, SR140333 and CGRP(8-37), prevented SLIGRL-induced MPO and damage score increases and permeability. In contrast, although the tight-junction blocker, 2,4,6-triaminopyrimidine, and the myosin L chain kinase inhibitor, ML-7, prevented SLIGRL-induced increase in permeability, they did not prevent MPO and damage score increases. Taken together our data show that both NO and capsaicin-sensitive afferent neurons are involved in PAR-2-mediated colonic inflammation and paracellular permeability increase. Nevertheless, the inflammation process is not a consequence of increased permeability which results at least in part from the activation of myosin L chain kinase.
...
PMID:Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability. 1268 65

We analysed the influence of aging on the acute effect of clenbuterol, a beta(2)-adrenoceptor agonist, on the vasoconstrictor response induced by electrical field stimulation in mesenteric arteries from young and old spontaneously hypertensive rats (SHRs). Clenbuterol increased the contraction elicited by electrical field stimulation in arteries from both groups, and this was prevented by propranolol. N(G)-nitro-L-arginine methyl ester (L-NAME) also increased the electrical field stimulation-elicited contractions in arteries from both age groups. However, pretreatment with capsaicin increased the electrical field stimulation-induced contractions in young SHRs, but did not modify it in old SHRs. In segments from young SHRs, the treatment with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37), induced an increase in the electrical field stimulation-induced vasoconstrictor response that was not modified by the subsequent addition of capsaicin. Addition of clenbuterol to L-NAME-treated segments from both groups further increased the response to electrical field stimulation. In segments from young SHRs, clenbuterol failed to increase the electrical field stimulation-induced response in the capsaicin-treated segments, but the response was increased by the subsequent addition of L-NAME. The addition of L-NAME to the clenbuterol-treated segments from old SHRs did not modify the enhanced electrical field stimulation response. Electrical field stimulation induced a similar tritium release in arteries from young and old SHRs preincubated with [3H]noradrenaline. In arteries from young SHRs, isoproterenol increased this release and the increase was abolished by propranolol. Clenbuterol increased the stimulated tritium overflow and exogenous noradrenaline response only in segments from old SHRs, and both effects were abolished by propranolol. To summarize and conclude, clenbuterol increased the electrical field stimulation-induced contraction in segments from both age groups. In young SHRs, clenbuterol seems to inhibit CGRP release, while in old SHRs, it increases the release of and response to noradrenaline and decreases neuronal nitric oxide (NO) release.
...
PMID:Different effects of acute clenbuterol on vasomotor response in mesenteric arteries from young and old spontaneously hypertensive rats. 1269 12

Endogenous neuropeptides released from nociceptors can induce vasodilation and enhanced protein extravasation (neurogenic inflammation). The role of nitric oxide (NO) in the induction of neurogenic inflammation is controversial. In this study, dermal microdialysis was used in awake humans (n = 39) to deliver substance P (SP; 10(-7) and 10(-6)M) or calcitonin gene-related peptide (CGRP; 5 x 10(-7)M and 2 x 10(-6)M). Neuropeptide-induced local and axon reflex erythema was assessed by laser Doppler imaging. Total protein concentration in the dialysate was measured to quantify local protein extravasation. The responses were assessed in the absence and the presence of the nitric oxide synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME) added to the perfusate at concentrations of 5, 10 or 20 mM. L-NAME (5 mM) applied via the dialysis catheters reduced local blood flow by approximately 30%. In addition, L-NAME inhibited SP-induced vasodilation by about 40% for 10(-7)M SP and 30% for 10(-6)M SP (n = 11, p < 0.01). In contrast, CGRP-induced vasodilation was only marginally inhibited by L-NAME. SP, but not CGRP, provoked a dose-dependent increase in protein extravasation. L-NAME (5 mM) inhibited this increase by up to 40% for both SP concentrations used (n = 11, p < 0.01). Higher concentrations of L-NAME did not further reduce SP- or CGRP-induced vasodilation or SP-induced protein extravasation. Exogenously applied SP induces vasodilation and protein extravasation, which is partly NO mediated, whereas CGRP-induced vasodilation appears to be NO independent.
...
PMID:The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin. 1280 46

Human and rodent studies have demonstrated that calcitonin gene-related peptide (CGRP), a potent vasodilator, relaxes uterine tissue during pregnancy but not during labor. The vascular sensitivity to CGRP is enhanced during pregnancy, compared to nonpregnant human uterine arteries. In the present study, we hypothesized that uterine artery relaxation effects of CGRP are enhanced in pregnant rats compared to nonpregnant diestrus rats (NP-DE) and that several secondary messenger systems are involved in this process. We also hypothesized that the expression of CGRP-A receptor components, calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1), and CGRP-B receptors are greater in pregnant rats. For vascular relaxation studies, uterine arteries from either NP-DE or Day 18 pregnant rats were isolated, and responsiveness of the vessels to CGRP was examined with a small vessel myograph. CGRP-A and CGRP-B receptor expressions were assessed by RT-PCR and Western immunoblotting, respectively. CGRP (10(-10)--10(-7) M) produced a concentration-dependent relaxation of norepinephrine-induced contractions in both NP-DE and Day 18 pregnant rat uterine arteries. Pregnancy increased the vasodilator sensitivity to CGRP significantly (P < 0.05) compared to NP-DE rats. CGRP receptor antagonist, CGRP8-37, inhibited CGRP-induced relaxation of pregnant uterine arteries. The CGRP-induced relaxation was not affected by NG-nitro-l-arginine methyl ester (L-NAME) (nitric oxide inhibitor, 10(-4) M) but was significantly (P < 0.05) attenuated by inhibitors of guanylate cyclase (ODQ, 10(-5) M) and adenylate cyclase (SQ 22536, 10(-5) M). CGRP-induced vasorelaxation was significantly (P < 0.05) attenuated by potassium channel blockers KATP (glybenclamide, 10(-5) M) and K(CA) (tetraethylammonium, 10(-3) M). The expression of CRLR and RAMP1 was significantly (P < 0.05) elevated during pregnancy compared to nonpregnant diestrus state (NP-DE). However, CGRP-B receptor proteins in uterine arteries were not altered with pregnancy compared to those of NP-DE. These studies suggest that CGRP-induced increases in uterine artery relaxation may play a role in regulating blood flow to the uterus during pregnancy and, therefore, in fetal growth and survival.
...
PMID:Mechanisms involved in calcitonin gene-related Peptide-induced relaxation in pregnant rat uterine artery. 1285

We examined whether capsaicin-sensitive sensory neurons might be involved in the increase in the gastric tissue level of prostaglandins, thereby contributing to the reduction of water immersion restraint stress (WIR)-induced gastric mucosal injury in rats. Gastric tissue levels of calcitonin gene-related peptide (CGRP), 6-keto-PGF1alpha, and PGE2 were transiently increased 30 min after WIR. These increases were significantly inhibited by subcutaneous injection of capsazepine (CPZ), a vanilloid receptor antagonist, and by functional denervation of capsaicin-sensitive sensory neurons induced by the administration of high-dose capsaicin. The administration of capsaicin (orally) and CGRP (intravenously) significantly enhanced the WIR-induced increases in the gastric tissue level of prostaglandins 30 min after WIR, whereas CGRP-(8-37), a CGRP receptor antagonist, significantly inhibited them. Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of nitric oxide (NO) synthase (NOS), and that with indomethacin inhibited the WIR-induced increases in gastric tissue levels of prostaglandins, whereas either pretreatment with aminoguanidine (AG), a selective inhibitor of the inducible form of NOS, or that with NS-398, a selective inhibitor of cyclooxygenase (COX)-2, did not affect them. CPZ, the functional denervation of capsaicin-sensitive sensory neurons, and CGRP-(8-37) significantly increased gastric MPO activity and exacerbated the WIR-induced gastric mucosal injury in rats subjected to 4-h WIR. The administration of capsaicin and CGRP significantly increased the gastric tissue levels of prostaglandins and inhibited both the WIR-induced increases in gastric MPO activity and gastric mucosal injury 8 h after WIR. These effects induced by capsaicin and CGRP were inhibited by pretreatment with L-NAME and indomethacin but not by pretreatment with AG and NS-398. These observations strongly suggest that capsaicin-sensitive sensory neurons might release CGRP, thereby increasing the gastric tissue levels of PGI2 and PGE2 by activating COX-1 through activation of the constitutive form of NOS in rats subjected to WIR. Such activation of capsaicin-sensitive sensory neurons might contribute to the reduction of WIR-induced gastric mucosal injury mainly by inhibiting neutrophil activation.
...
PMID:Contribution of capsaicin-sensitive sensory neurons to stress-induced increases in gastric tissue levels of prostaglandins in rats. 1289 32

The vasorelaxant effects of N-[4-O-[2-methoxy, phenoxyethylaminobutyl]-3-methoxy benzyl]-nonamide (VOA), a novel capsaicin derivative, and associated releasing activities of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) were investigated in this study. Systemic administration of VOA decreased blood pressure and heart rate in a dose-dependent manner in both normotensive as well as spontaneously hypertensive rats. Nw-nitro-L-arginine methyl ester (L-NAME), glibenclamide, and capsazepine inhibited VOA-induced hypotension. In phenylephrine-precontracted rat aortic rings and mesenteric arteries with intact endothelium, VOA caused a concentration-dependent relaxation. This relaxation was reduced after endothelium was removed or pretreated with L-NAME, methylene blue, 1 H-[1,2,4]oxidazolol [4,3-a] quinoxalin-1-one, tetraethylammonium, glibenclamide, CGRP (8-37), or capsazepine, respectively. In endothelially denuded vessel rings, tetraethylammonium, glibenclamide, CGRP (8-37), and capsazepine also reduced VOA-induced relaxation. In high potassium (80 mmol/L)-precontracted rat aortic rings with intact endothelium, VOA failed to induce relaxation. VOA induced a concentration-dependent increase of CGRP-like enzyme immunoreactivity, which was also significantly inhibited by capsazepine. In human umbilical vein endothelial cells, VOA increased NO release and guanosine-3', 5'-cyclic monophosphate level, which were significantly inhibited by L-NAME. The Western blot analysis on human umbilical vein endothelial cells indicated that VOA increased the expression of endothelium nitric oxide synthase. In conclusion, VOA might exert its relaxation effects in rat vascular smooth muscle through the CGRP/KATP channel and the NO/ cGMP pathway.
...
PMID:A novel capsaicin derivative VOA induced relaxation in rat mesenteric and aortic arteries: involvement of CGRP, NO, cGMP, and endothelium-dependent activities. 1450 37

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>