Halothane anesthesia suppresses reflex tachycardia caused by calcitonin gene-related peptide in dogs

Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg⁻¹ of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg⁻¹) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg⁻¹ CGRP but remained unchanged at the 40 μg·kg⁻¹ infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg⁻¹. In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg⁻¹ produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia. This study was presented in part at the 39th annual meeting of the Japan Society of Anesthesiology, Fukuoka, April 1992, and at the annual meeting of the American Society of Anesthesiologists, New Orleans, October 1992     

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。     

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.     

Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development

Amylin and calcitonin gene-related peptide (CGRP) are homologous 37 amino acid peptides that are found in the circulation. Both peptides belong to the calcitonin family. Similar to calcitonin, amylin and CGRP inhibit osteoclast activity, although they are much less potent than calcitonin. Calcitonin is known to act on the latter stages of osteoclast development, inhibiting the fusion of committed preosteoclasts to form mature multinucleated cells; however, whether or not calcitonin acts earlier in the formation of the precursor osteoclasts is controversial. The question of osteoclast development has never been examined with respect to amylin and CGRP. These issues are addressed in the present study. We studied the effects of calcitonin (salmon and rat), amylin (human and rat), and CGRP (human and rat) in mouse bone marrow cultures stimulated to generate osteoclasts using 1alpha,25-dihydroxyvitamin D3. Calcitonin dose-dependently decreased the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells as well as TRAP-positive mono-/binucleated cells at concentrations >10(-13) mol/L. Amylin and CGRP showed similar effects at concentrations >10(-9) mol/L. In addition, calcitonin substantially reduced the ratio of TRAP-positive multinucleated to mono-binucleated cells, indicating an effect on fusion of osteoclast precursors. The present data establish that this family of peptides not only acts on mature osteoclasts but also inhibits their development in bone marrow cultures. This activity is shared by amylin and CGRP. The much greater potency of calcitonin than amylin and CGRP is consistent with the action of these peptides being mediated by calcitonin receptors.     

Posttreatment with adenovirus-mediated gene transfer of calcitonin gene-related peptide to reverse cerebral vasospasm in dogs

OBJECT: Gene transfer to cerebral vessels is a promising new therapeutic approach for cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was undertaken to explore whether a delayed treatment with adenovirus encoding the prepro-calcitonin gene-related peptide (CGRP), 2 days after initial blood injection, reduces cerebral vasospasm in a double-hemorrhage model of severe vasospasm in dogs. METHODS: In 20 dogs, arterial blood was injected into the cisterna magna on Days 0 and 2. Thirty minutes after the second blood injection, the animals received either adenovirus encoding the prepro-CGRP gene (AdCMVCGRP-treated group, eight dogs) or adenovirus encoding the beta-galactosidase gene (AdCMVbeta gal-treated group, six dogs) under the cytomegalovirus (CMV) promoter. One group of dogs did not receive treatment and served as controls (control SAH group, six dogs). Angiography was performed on Days 0 and 7 to assess cerebral vasospasm. On Day 7 following angiography, the animals were killed and their brains were stained with X-gal to detect the distribution of gene expression. Cerebrospinal fluid (CSF) was also tested for CGRP immunoreactivity. Severe vasospasm was observed in control SAH dogs on Day 7, and the mean basilar artery (BA) diameter was 53.4 +/- 5.5% of the value measured on Day 0. Treatment with AdCMVbeta gal did not alter vasospasm (the BA diameter was 55 +/- 3.9% of that measured on Day 0). The leptomeninges and adventitia of the BAs of dogs treated using AdCMVbeta gal demonstrated positive staining with X-gal. High levels of CGRP were measured in CSF from dogs that received AdCMVCGRP. In the group treated with AdCMVCGRP, vasospasm was significantly reduced (the BA diameter was 78.2 +/- 5.3% of that measured on Day 0, p < 0.05 compared with the control SAH group and the AdCMVbeta gal group). CONCLUSIONS: In a model of severe vasospasm in dogs, gene transfer of CGRP after injection of blood attenuated cerebral vasospasm after SAH.     

Evaluation of postoperative exocrine pancreatic function using chymotrypsin labile peptide

The assessment of exocrine pancreatic function by the oral administration of a chymotrypsin labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) has proved to be an easy and reliable test of exocrine pancreatic function. It has the additional advantage that it can be used to study exocrine pancreatic function in all operative cases, even after gastrointestinal reconstruction. The recovery of p-aminobenzoic acid (PABA) correlates significantly with parameters of the PZ/CCK secretin (PS) test. Following Billroth II gastrectomy, the recovery of PABA decreased to 39.8±3.2% to weeks after and to 45.4±4.5% one to two months after operation, significantly lower than the 80.6±3.4% in normal subjects. In cases of cancer of the head of the pancreas, the exocrine function was 44.0±3.7%, and decreased to 17.5±3.0% after total pancreatectomy. Thus, BT-PABA enables a pertinent evaluation of pancreatic function in postoperative patients with various types of gastrointestinal reconstruction and also in cases when the PS test cannot be feasibly used.     

Effects of epidural analgesia on plasma calcitonin gene-related peptide

The effects of epidural analgesia on plasma calcitonin gene-related peptide (CGRP) values during and after hysterectomy were investigated in 14 healthy patients. In seven patients who received general anaesthesia alone for pelvic surgery, there were no significant changes in plasma CGRP concentrations. In the remaining patients, who received extensive epidural blockade in addition to general anaesthesia, there were again no significant changes in plasma CGRP values. This was in spite of profound sympathetic blockade, as shown by marked hypotension and a significant decline in plasma catecholamines. The epidural group of patients showed the expected attenuation of the glucose, cortisol and growth hormone responses to surgery. The results show that circulating CGRP is unlikely to be involved in the modulation of peripheral vascular tone during pelvic surgery under either general or epidural anaesthesia.     

Relaxant effect of calcitonin gene-related peptide on cerebral arterial spasm induced by experimental subarachnoid hemorrhage in dogs

This study examines the relaxant effect of calcitonin gene-related peptide (CGRP), a 37-amino acid peptide with a potent vasodilator action, on cerebral arterial spasm after subarachnoid hemorrhage (SAH). The spasm was induced by injecting autologous arterial blood percutaneously into the cisterna magna in adult mongrel dogs. The single-injection model of SAH was produced by injection of 1.0 ml/kg body weight of blood (on Day 0), and the double-injection model involved two successive injections of 0.5 ml/kg body weight of blood made 48 hours apart (on Day 0 and Day 2). On vertebral angiograms, arterial narrowing of the major cerebral arteries was most prominent on Day 3 after SAH in the single-injection model and on Day 7 in the double-injection model. When 10(-10) mol/kg of CGRP was administered intracisternally in the single-injection model on Day 3, the diameter of the spastic cerebral arteries, as determined by angiography, recovered to normal. After intracisternal administration of 10(-11) to 2 X 10(-10) mol/kg of CGRP on Day 7 in double-injection models, spastic cerebral arteries dilated in a dose-dependent manner. The dilatory effect of CGRP continued for a few hours after administration. The results suggest that CGRP injected intracisternally may reverse cerebral arterial spasm after SAH.     

肢体负压对动脉闭塞犬血浆内皮素和降钙素基因相关肽的影响

目的观察肢体负压(LNP)对肢体动脉闭塞犬血浆内皮素(ET)和降钙素基因相关肽(CGRP)的影响,以探讨肢体负压的作用机理.方法犬15只,分治疗组10只和对照组5只,采用切断左后肢股动脉分支,动脉腔内置入螺旋状金属丝的方法,制作肢体动脉闭塞模型.2周后,治疗组行患肢负压治疗,连续10 d;对照组不做负压治疗.于模型制作前、制作后2周及负压治疗10 d时,用放射免疫分析法检测患肢股静脉血浆ET及CGRP水平.结果治疗组经负压治疗后,血浆ET水平显著低于治疗前(P<0.01),血浆CGRP水平显著高于治疗前(P<0.01),两者呈负相关;而对照组无明显变化(P>0.05).结论肢体负压可显著降低肢体动脉闭塞犬的血浆ET水平,提高CGRP水平.     

Release and effects of calcitonin gene-related peptide in myocardial ischaemia

This thesis is based on the following papers, which will be referred to by their Roman numerals. I. Franco-Cereceda A, Källner G, Lundberg JM: Capsazepine-sensitive release of calcitonin gene-related peptide from C-fibre afferents in the guinea-pig heart by low pH and lactic acid. Eur J Pharmacol 1993;238:311-316. II. Franco-Cereceda A, Källner G, Lundberg JM: Cyclo-oxygenase products released by low pH have capsaicin-like actions on sensory nerves in the isolated guinea pig heart. Cardiovasc Res 1994;28:365-369. III. Källner G, Franco-Cereceda A: Attenuation of low pH-, but not capsaicin- or PGI-evoked CGRP-release by endothelium removal using saponin. Acta Physiol Scand 1995;155:251-256. IV. Källner G, Franco-Cereceda A: Ion channels involved in the release of calcitonin generelated peptide by low pH, prostacyclin and capsaicin in the isolated guinea-pig heart. Eur J Pharmacol 1998;in press. V. Källner G, Gonon A, Franco-Cereceda A: Calcitonin gene-related peptide in myocardial ischaemia and reperfusion in the pig. Cardiovasc Res 1998;38:493-499. VI. Källner G, Franco-Cereceda A: Aggravation of myocardial infarction in the porcine heart by capsaicin-induced depletion of calcitonin gene-related peptide (CGRP). J Cardiovasc Pharmacol , accepted for publication. VII. Källner G, Öwall A, Franco-Cereceda A: Myocardial outflow of calcitonin gene-related peptide in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass. Submitted for publication.     

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.     

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.     

Binding of calcitonin and calcitonin gene-related peptide to calvarial cells and renal cortical membranes

Binding of calcitonin (CT) and calcitonin gene-related peptide (CGRP) to rat hemicalvariae and renal membranes was examined in an effort to determine whether CT and CGRP interact with the same bone cell binding site, and to see whether the binding pattern was similar for bone and renal cortex. Specific binding of 125I-salmon CT to rat calvariae was inhibited by unlabeled salmon, porcine, or human CT, but not by rat CGRP. Binding of 125I-rat CGRP to calvariae was inhibited by CGRP and high doses of salmon CT, but not by human or porcine CT. Binding of 125I-salmon CT to renal membranes was inhibited by unlabeled salmon CT or rat CGRP, but no specific binding of 125I-rat CGRP could be detected. The results suggest that separate bone cell receptors for CT and CGRP exist and that CGRP can interact with renal receptors for CT.