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 共查询到10条相似文献,搜索用时 203 毫秒
1.
S Akiyama  H Kawasaki  A Shimogai  Y Kurosaki 《Peptides》2001,22(11):1887-1893
We have reported that the rat mesenteric resistance artery has innervation of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRPergic nerves). We also demonstrated that adrenomedullin (AM) causes mesenteric vasodilation through activation of CGRP receptors. The present study was designed to examine the effect of AM on neurotransmission of CGRPergic nerves in rat mesenteric arteries. In preconstricted preparations without endothelium, periarterial nerve stimulation (PNS, 1 and 2 Hz) induced a frequency-dependent vasodilation. A bolus injection of CGRP (10 pmol) into the perfusate also caused a vasodilation. AM (0.1 to 10 nM) concentration-dependently caused 40% to 60% inhibition of the PNS-induced vasodilation, but AM did not attenuate vasodilation induced by exogenous CGRP injection. The inhibitory effect of AM (10 nM) on PNS-induced vasodilation was further potentiated by CGRP [8-37] (CGRP receptor antagonist, 50 nM), which attenuated the vasodilator response to the CGRP injection. Combined perfusion of AM [22-52] (AM receptor antagonist, 10 to 100 nM) resulted in further inhibition of PNS-induced neurogenic vasodilation without affecting the vasodilator response to the CGRP injection. CGRP [8-37] but not AM [22-52] antagonized vasodilation induced by AM perfusion. These findings suggest that AM presynaptically inhibits neurotransmission of CGRPergic nerves, probably decreasing CGRP release, via receptors different from CGRP receptors.  相似文献   

2.
The effect of perivascular nerve stimulation (PNS) on the release of calcitonin gene-related peptide (CGRP) was examined by radioimmunoassay (RIA) in isolated, perfused rat mesenteric arteries. The released CGRP-like immunoreactivity (CGRP-LI) was identified to be CGRP itself and its oxidized form by combined analysis with RIA and high performance liquid chromatography. CGRP-LI was localized in the perivascular nerves of the large mesenteric artery and its branches. In the preparation precontracted by methoxamine, and perfused with a solution containing guanethidine, an adrenergic neuron blocker, PNS induced vasodilator responses and an increase of CGRP-LI in the perfusate in a frequency-dependent manner. Both the responses were attenuated by tetrodotoxin (10(-6) M), suggesting that they were neurogenic in origin. Removal of Ca2+ from the perfusing solution also abolished the PNS-induced release of CGRP-LI. These findings suggest that CGRP plays a transmitter role in the neurogenic vasodilation in the rat mesenteric vascular bed.  相似文献   

3.
In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) increased amylase release 2-fold, salmon calcitonin had an efficacy of only 44% of that of CGRP and [Tyr0]CGRP(28-37) and human calcitonin had no actions. [Tyr0]CGRP(28-37), but not human calcitonin, antagonized the actions of CGRP in pancreatic acini with an IC50 of 3 microM. [Tyr0]CGRP(28-37) produced a parallel rightward shift in the dose-response curve for CGRP-stimulated amylase secretion. The inhibition was specific for CGRP and was reversible. Studies with 125I-CGRP demonstrated that CGRP, salmon calcitonin and [Tyr0]CGRP, but not human calcitonin, interacted with CGRP receptors on pancreatic acini. These results indicate that various CGRP-related peptides demonstrate different relationships between their abilities to occupy the CGRP receptor and to affect biologic activity, with CGRP itself being a full agonist, salmon calcitonin a partial agonist, [Tyr0]CGRP(28-37) a competitive antagonist, and human calcitonin having no actions.  相似文献   

4.
P Rovero  S Giuliani  C A Maggi 《Peptides》1992,13(5):1025-1027
The activity of short C-terminal fragments of human alpha calcitonin gene-related peptide (CGRP), CGRP(19-37), and CGRP(23-37), and of the N-terminally acetylated (Ac) derivative, AcCGRP(19-37), has been investigated in the guinea pig isolated left atria (electrically driven) for their ability to antagonize the positive inotropic effect of human alpha CGRP. All the peptides tested produced a rightward displacement of the curve to the agonist without depressing the maximal response: apparent pA2 values were 5.39 and 4.81 for CGRP(19-37) and CGRP(23-37), respectively, as compared to 6.81 for CGRP(8-37). AcCGRP(19-37) was a more potent antagonist than the parent peptide, with an apparent pA2 value of 6.03.  相似文献   

5.
Alteration of cochlear blood flow may be involved in the etiology of inner ear disorders like sudden hearing loss, fluctuating hearing loss and tinnitus. The aim of the present study was to localize the vasodilator calcitonin gene-related peptide (CGRP) and to identify CGRP receptors and their signaling pathways in the gerbil spiral modiolar artery (SMA) that provides the main blood supply of the cochlea. CGRP was localized in perivascular nerves by immunocytochemistry. The vascular diameter and cytosolic Ca2+ concentration [Ca2+]i in the smooth muscle cells were measured simultaneously with videomicroscopy and fluo-4-microfluorometry. Calcitonin receptor-like receptor (CRLR) mRNA was identified by RT-PCR as a specific 288 bp fragment in total RNA isolated from the vascular wall. The SMA was preconstricted by a 2-min application of 1 nM endothelin-1 (ET1). CGRP, forskolin, and dibutyryl-cAMP caused a vasodilation (EC50 = 0.1 nM, 0.3 mM, and 20 mM). CGRP and forskolin caused an increase in cAMP production and a transient decrease in the [Ca2+]i. The CGRP-induced vasodilation was antagonized by CGRP8-37 (KDB = 2 mM). The K+-channel blockers iberiotoxin and glibenclamide partially prevented the CGRP- or forskolin-induced vasodilations but failed to reverse these vasodilations. These results demonstrate that CGRP is present in perivascular nerves and causes a vasodilation of the ET1-preconstricted SMA. The data suggest that this vasodilation is mediated by an increase in the cytosolic cAMP concentration, a transient activation of iberiotoxin-sensitive BK and glibenclamide-sensitive KATP K+ channels, a transient decrease in the [Ca2+]i and a long-lasting Ca2+ desensitization.  相似文献   

6.
Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.  相似文献   

7.
The physiological significance of calcitonin gene-related peptide (CGRP) during biomineralization was investigated by assessing the effect of human CGRP on the carbonic anhydrase activity in gill membranes of the pearl oyster, Pinctada margaritifera. Salmon CT and human CGRP were able to induce a 150% increase of the basal activity. No additive effect was observed suggesting that both activities are mediated by the same receptor. The CGRP-stimulated effect was specific as demonstrated by the inhibition produced by the CGRP antagonist, hCGRP8-37. So, CGRP by its specific action on gill carbonic anhydrase controls the calcification process, an ancient role both in invertebrates and non-mammalian vertebrates.  相似文献   

8.
Martinez V  Wang L  Taché Y 《Peptides》2006,27(6):1376-1382
The effects of intravenous (iv) adrenomedullin (AM) on gastric emptying were investigated in conscious rats. AM induced a maximal 50% inhibition of gastric emptying at a dose of 1.2 nmol/kg. AM was about two-fold less potent than alpha-calcitonin gene-related peptide (alpha-CGRP), which induced a similar 50% maximal inhibition of gastric emptying at 0.6 nmol/kg. Delayed gastric emptying induced by i.v. AM and alpha-CGRP was prevented by peripheral injection of the selective CGRP1 antagonist, CGRP8-37, and by pretreatment with indomethacin, while not altered by blockade of the sympathetic nervous system with propranolol. These data indicate that peripheral AM inhibits gastric emptying through the interaction with CGRP8-37 -sensitive receptors, likely CGRP1 receptors, and the recruitment of prostaglandin-dependent mechanisms.  相似文献   

9.
降钙素基因相关肽(CGRP)mRNA在大鼠淋巴细胞中的表达   总被引:10,自引:0,他引:10  
Xing LY  Xing YT  Tang YM  Guo JX  Wang X 《生理学报》1998,50(4):423-430
最近,我们研究发现大鼠胸腺和淋巴结淋巴细胞中存在降钙素基因相关肽(CGRP)样免疫反应活性。应用人工合成的可特异扩增降钙素/降钙素基因相关肽基因部分片断的寡核苷酸引物,通过逆转录-多聚酶链反应(RT-PCR),检测在大鼠脊髓背根神经节、胸腺细胞及肠系膜淋巴结淋巴细胞中是否存在CGRP mRNA,进一步研究大鼠淋巴细胞能否合成CGRP。结果显示,通过RT-PCR从脊髓背根神经节(阳性对照)、胸腺和淋  相似文献   

10.
We have investigated the effect of the C-terminal fragment of human calcitonin gene-related peptide (human-CGRP8-37), a CGRP antagonist, on alpha-CGRP and salmon Calcitonin (sCT)-induced inhibition of gastric acid secretion stimulated by pentagastrin (24 nmol kg-1 h-1 i.v.) and gastric lesions induced by acetylsalycilic acid (ASA; 25 mM) in rats anaesthetized with urethane. Close intra arterial infusion of alpha-CGRP (2-5 nmol kg-1) and sCT (5 nmol kg-1) produced a reduction in gastric acid hypersecretion induced by pentagastrin. The concomitant infusion with human-CGRP8-37 (10 nmol kg-1) reversed the effect of both agonists. ASA-ulcers were reduced in a dose-dependent manner by infusion of alpha-CGRP (1-2 nmol kg-1 i.a.), but not by sCT (10 nmol kg-1 i.a.). Human-CGRP8-37 at a dose of 10 nmol kg-1 i.a. was unable to reverse the alpha-CGRP antiulcer effect. An higher dose of human-CGRP8-37 (50 nmol kg-1 i.a.) showed agonistic properties reducing ASA ulcers. These results suggest that the inhibitory effects of alpha-CGRP on stimulated acid secretion and aspirin ulcers are mediated by different mechanisms and/or different receptors.  相似文献   

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