Role of spinal afferents and calcitonin gene-related peptide in the postoperative gastric ileus in anesthetized rats.

OBJECTIVE: The object of this study was to investigate the mechanisms of postoperative gastric ileus in an experimental model of abdominal surgery in anesthetized rats. SUMMARY BACKGROUND DATA: Sensory neurons partly mediate postoperative gastric ileus. Among other neuropeptides, sensory neurons contain calcitonin gene-related peptide (CGRP) and release CGRP in response to noxious stimulation. Because CGRP inhibits gastric motility, it was hypothesized that abdominal surgery stimulates sensory neurons, which then releases CGRP, thereby inhibiting gastric motility. METHODS: Postoperative ileus was induced by abdominal surgery. Gastric corpus motility was measured by an intragastric catheter. CGRP action was blocked by CGRP immunoneutralization or by a CGRP receptor antagonist. Spinal sensory neurons were ablated by application of a sensory neurotoxin (capsaicin) to the celiac and superior mesenteric ganglia. RESULTS: Abdominal surgery decreased gastric corpus motility in the first 5 minutes after abdominal surgery by 59 +/- 5% and by 24 +/- 4% during the 1st postoperative hour. Capsaicin pretreatment of the celiac and superior mesenteric ganglia, CGRP immunoneutralization, or CGRP receptor antagonism reversed the postoperative decrease in gastric corpus motility during the 1st postoperative hour by 50%, 100%, and 59%, respectively. CONCLUSIONS: These data indicate that spinal sensory neurons and CGRP partly mediate postoperative gastric ileus. CGRP may be released from spinal sensory neuron terminals in the celiac and superior mesenteric ganglia as part of an extraspinal intestinogastric inhibitory reflex activated by abdominal surgery.     

Renal mesangium is a target for calcitonin gene-related peptide

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.     

Cardiovascular action of calcitonin gene-related peptide in humans

Summary 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<0.01) and lowered arterial systolic and diastolic pressures by 26 mm Hg and 20 mm Hg, respectively (P<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<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<0.05). Further-more, CGRP (12.7 nmol) reduced the preejection period and duration of the electromechanical systole by 26 msec and 66 msec, respectively (P<0.001 andP<0.01), presumably acting as positive inotropic agent. Labetalol, blocking adrenergic receptors, obliterated these inotropic effects, whereas the positve chronotropic and hypotensive actions of CGRP remained unchanged.     

降钙素基因多肽对骨代谢的影响

根据骨质疏松的发病机制不同,可分为原发性骨质疏松和继发性骨质疏松,原发性骨质疏松又可分为绝经性骨质疏松和老年性骨质疏松。骨质疏松是由多种发病因素共同作用的结果,在各型骨质疏松中,降钙素均发挥重要的调节作用。近年研究发现某些神经、血管活性肽,如降钙素基因多肽(Calcitonin gene-related peptide,CGRP）,在结构和功能上与降钙素具有一定的相似性。本文将降钙素基因多肽对骨代谢影响的相关研究进展作以下综述。     

Plasma calcitonin gene-related peptide and atrial natriuretic peptide levels during resection of pheochromocytoma.

Calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) are potent hypotensive agents. To determine if they play a counterregulatory role in catecholamine excess in patients with pheochromocytoma, plasma levels were measured in four patients undergoing resection of sporadically occurring tumors. Each patient was prepared with phenoxybenzamine hydrochloride (Dibenzyline); two patients also received propranolol. Blood was obtained for plasma levels of epinephrine, norepinephrine, CGRP, and ANP at induction of anesthesia, skin incision, tumor manipulation, tumor removal, and 24 hours after operation. Baseline plasma norepinephrine and epinephrine levels were markedly elevated and increased significantly with tumor manipulation and decreased significantly 24 hours after operation. CGRP and ANP levels were slightly elevated throughout but did not change significantly with tumor manipulation or early after tumor resection. Circulating CGRP and ANP do not appear to have an acute counterregulatory role in catecholamine excess in patients with pheochromocytoma but may exert some influence on postoperative hypotension after tumor removal.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

降钙素基因相关肽在预处理心肌保护中机制的研究进展

近年来发现一种新的神经肽即降钙素基因相关肽(calcitonin gene related peptide,CGRP)具有强心、舒张血管的作用,是目前研究的热点.CGRP能防止心肌缺血/再灌注损伤,在预处理即时和延时心肌保护中的研究很多,但是其具体的机制仍不清楚,仍需要进一步的研究.现主要对CGRP在预处理心肌保护中的作用作一综述.     

Serum calcitonin gene-related peptide levels in untreated prostate cancer patients

BACKGROUND: The role of calcitonin gene-related peptide (CGRP) in prostate cancer has not been fully understood. Moreover, the serum CGRP level in prostate cancer patients has never been reported. We measured the serum CGRP levels in untreated prostate cancer patients to elucidate its clinical significance. MATERIALS AND METHODS: We used 36 serum samples from prostate cancer patients. All patients had never received any treatment. Serum CGRP was measured by immunoradiometric assay, and we analysed the association between serum CGRP level and clinicopathological factors. RESULTS: Serum CGRP levels in the patients with higher clinical stages and histological grade were significantly higher than in those with lower stages and grade, respectively. But the levels did not correlate with the patient's age, liver or renal functions, serum prostate-specific antigen levels. CONCLUSION: Serum CGRP levels were significantly elevated in the patients with high grade or high stage untreated prostate cancer patients. Measurement of the serum CGRP may be a useful predictor of staging or grading of prostate cancer in the untreated prostate cancer patients.     

Calcitonin and calcitonin gene-related peptide in the human prostate gland

BACKGROUND: Calcitonin-related peptides have been found in the human prostate, and calcitonin (CT) and calcitonin gene-related peptide (CGRP) have been demonstrated in subpopulations of neuroendocrine (NE) cells. The purpose of this study was to determine the concentrations of CT and CGRP as well as the densities of NE cells in normal prostates, benign prostatic hyperplasia (BPH), and carcinoma of the prostate (CAP). METHODS: In 42 specimens of radical prostatectomy, the number of CT- and CGRP-immunoreactive NE cells in areas of normal and BPH tissue was determined, and compared with CAP tissue using immunocytochemistry. In addition, by radioimmunoassay (RIA), tissue levels of CT and CGRP were analyzed in extracts from areas of normal, BPH, and CAP tissue, as verified by adjacent histologic sections. RESULTS: A significant decrease in CT-immunoreactive NE cells was observed in hyperplastic nodules of BPH in comparison to normal tissue. These findings were in parallel with a significant reduction in tissue CT level in BPH compared to normal tissue. There was also a marked, but statistically nonsignificant, reduction in CT levels in CAP tissue. In contrast, levels of CGRP in BPH and CAP tissue did not show any significant differences compared to normal tissue. CONCLUSIONS: CT and CGRP are present in NE cells of the human prostate. Calcitonin levels are significantly reduced in BPH, in parallel with a decreased number of CT-immunoreactive NE cells, whereas no significant changes in tissue levels of CGRP were observed. The functional significance of these findings is discussed.     

Localization of calcitonin gene-related peptide within the genitofemoral nerve in immature rats.

BACKGROUND/PURPOSE: Calcitonin gene-related peptide (CGRP) has been proposed to influence migration and testicular descent by release from the genitofemoral nerve. The site of CGRP within the nerve has been controversial, with conflicting views on whether CGRP is synthesised and released from the motor nerves. METHODS: The genitofemoral nerve (GFN) was retrogradely labelled by fluorescent dye (DAPI) in 25 Sprague-Dawley rats (days 5, 16, and 31, n = 8 in each group; day 35, n = 1). Spinal cords and dorsal root ganglia (DRG) were removed two to three days later and sectioned for immunofluorescence. Substance P and CGRP-containing cells were labelled with fluorescein-linked antibodies. Specimens were examined by double fluorescence to identify cells with both markers. RESULTS: The motor nucleus of the GFN contained 119 cells on day 7 and 284 cells by days 19 through 34. A prominent band of CGRP-containing fibers, arising from the dorsal horn, synapsed with the GFN motor nucleus itself. CGRP-labelled GFN cells were found in the DRG by double labelling. CONCLUSIONS: CGRP from the GFN may affect gubernacular migration by release from the sensory nerves, rather than motor nerves as previously thought. The GFN motor nucleus receives CGRP-containing innervation from the dorsal horn, which may form part of the cremasteric reflex.     

Splanchnic and cerebral vasodilatory effects of calcitonin gene-related peptide I in humans.

The ability of synthetic human calcitonin gene-related peptide (CGRP I) to act as an arterial vasodilator was tested in healthy men by measuring arterial blood flow parameters in carotid, superior mesenteric, celiac, and femoral vessels. Calculated volume flow was significantly increased (140 +/- 21% of basal) in the SMA with a 2-ng/kg/min infusion of CGRP. Carotid artery volume flow increased dose dependently (96 +/- 6%, 122 +/- 15%, 135 +/- 15% of basal, respectively, with 2, 4, or 8 ng/kg/min). With steady-state infusion, carotid and superior mesenteric arterial flow parameters remained significantly elevated for 30 minutes after cessation of peptide administration. Blood pressure was unchanged. Pulse increased dose dependently. Arterial diameters were unchanged, implying activity at the arteriolar level.     

Demonstration of calcitonin gene-related peptide receptors in the gubernaculum by computerized densitometry.

The gubernaculum appears to guide inguinoscrotal testicular descent by migration into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) has been found in the scrotal branches of the genitofemoral nerve of neonatal rats, and is known to stimulate gubernacular motility in vitro. This study aimed to identify CGRP receptors in the gubernaculum, which should be present if CGRP mediates gubernacular migration toward the scrotum. Gubernacular sections from neonatal male rats were incubated with [125I]-human CGRP as well as a variety of unlabeled neuropeptides. By using computerized densitometry, the quantitation of CGRP binding derived from in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. The binding analysis showed a single class of sites with a dissociation constant (Kd) of 2.13 nmol/L and a receptor density of 27.4 fmol/mg polymer. These results endorse the hypothesis that CGRP released from the nerve acts directly on the cremaster via its own receptors, which have not been described previously.