This study was to observe the effect and possible mechanism of somatostatin analogue octreotide (OCT) on cross excitation of adjacent segment of spinal nerve in rat. Cutaneous branches of T9-T13 spinal dorsal rami were chosen and dissected free for the following recording and stimulation. Only single unit fiber was used for recording, and the adjacent segment of nerve stem was used for antidromic electrical stimulation. To investigate the change of discharge rate and mechanical threshold, OCT and (or) somatostatin receptor antagonist cyclo-somatostatin (c-SOM) were applied to the receptive field following the antidromic electrical stimulation. The result showed that injection of OCT inhibited the increase of discharge rate and the decrease of mechanical threshold induced by the electrical stimulation (cross excitation); c-SOM reversed the effects of OCT. Application of c-SOM alone enhanced the cross excitation effects. The results suggest local application of somatostatin analogue OCT can inhibit the cross excitation between the two segments of spinal nerve by somatostatin receptor.
Animals ; Electric Stimulation ; Octreotide ; pharmacology ; Peptides, Cyclic ; pharmacology ; Rats ; Receptors, Somatostatin ; physiology ; Somatostatin ; analogs & derivatives ; Spinal Nerves ; drug effects

BACKGROUNDPreconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu (micro)-, delta (delta)- or kappa (kappa)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning.

METHODSThe rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective delta-, kappa- or micro-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2, 3, 5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats.

RESULTSThe EA preconditioning reduced brain infarct volume compared with the control rats (P = 0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P < 0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats (P = 0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P = 0.000).

CONCLUSIONRepeated EA preconditioning stimulates the release of enkephalins, which may bind delta- and micro-opioid receptors to induce the tolerance against focal cerebral ischemia.

Animals ; Brain Ischemia ; prevention & control ; Electroacupuncture ; Enkephalin, Methionine ; analysis ; Immunohistochemistry ; Ischemic Preconditioning ; Male ; Naltrexone ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, delta ; physiology ; Receptors, Opioid, mu ; physiology ; Somatostatin ; analogs & derivatives ; pharmacology

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.
Animal ; Aspirin/pharmacology* ; Cardiovascular Agents/pharmacology* ; Coronary Arteriosclerosis/pathology ; Coronary Arteriosclerosis/immunology* ; Coronary Vessels/pathology ; Coronary Vessels/drug effects ; Heart/drug effects* ; Heart Transplantation/immunology* ; Immunohistochemistry ; Mice ; Mice, Inbred Strains ; Myocardium/pathology ; Myocardium/immunology ; Oligopeptides/pharmacology* ; Somatostatin/pharmacology ; Somatostatin/analogs & derivatives* ; Transplantation, Homologous/immunology ; Tropomyosin/metabolism

Esophageal and Gastric Varices ; drug therapy ; etiology ; Female ; Gastrointestinal Agents ; therapeutic use ; Gastrointestinal Hemorrhage ; drug therapy ; etiology ; Glucagon ; blood ; Humans ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Nitric Oxide ; blood ; Octreotide ; therapeutic use ; Somatostatin ; analogs & derivatives

Recently various peptide receptors which displayed the highest binding affinity and specificity with their peptide ligands by ligand-receptor have been exploited to develop drug delivery system which can directionally deliver drug to targeted cell. It is significant to study and applicate, including targeted drug delivery system mediated by bombesin receptor, somatostatin receptor, SynB3 receptor, LH-RH receptor and other peptide receptor, et al. Several small peptide fragments were selected as carriers radicals combining doxorubicin, 2-pyrrolino-DOX, methotrexate, cis-platinum, and camptothecin to form hybrid cytotoxic analogs. These highly potent cytotoxic analogs have been designed as targeted anti-tumor agents for the treatment and study of various cancers that possess receptors for the carrier peptide.
Animals ; Antineoplastic Agents ; therapeutic use ; Doxorubicin ; analogs & derivatives ; therapeutic use ; Drug Delivery Systems ; Humans ; Neoplasms ; drug therapy ; metabolism ; Oligopeptides ; metabolism ; Pyrroles ; therapeutic use ; Receptors, Bombesin ; metabolism ; Receptors, LHRH ; metabolism ; Receptors, Somatostatin ; metabolism

OBJECTIVETo evaluate the value of (99 m)Tc-sandostatin scintigraphy in targeted diagnosis of pancreas carcinoma and the correlation with expression of somatostatin receptor (SSTR) reporter gene in tumor tissue.

METHODSNude mice bearing human pancreas carcinoma xenograft were established in advance. (99 m)Tc-sandostatin imaging was performed in 18 nude mice and tumor to normal tissue ratio (T/NT) was calculated. mRNA expression of SSTR1, SSTR2 and SSTR5 in tumor tissue was detected by RT-PCR.

RESULTSOut of 18 nude mice, 13 mice showed intense uptake of (99 m)Tc-sandostatin. Six hours after (99 m)Tc-sandostatin administration, the T/NT ratio was 2.53 +/- 0.84. Five mice showed negative findings, and the T/NT ratio was 1.04 +/- 0.06. Positive correlations were obtained between the T/NT ratio and the expression of SSTR1 and SSTR2 mRNA, especially SSTR2 (r = 0.807, P < 0.01).

CONCLUSIONHigh expression of SSTR1, SSTR2 and SSTR5 mRNA were found in human pancreas tumor xenograft in nude mice, especially SSTR2. There is a significant correlation between the tumor uptake of (99 m)Tc-sandostatin and SSTR2 mRNA level. This approach may allow SSTR-targeted diagnosis and therapy of human pancreas cancer.

Animals ; Genes, Reporter ; genetics ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Octreotide ; analogs & derivatives ; Organotechnetium Compounds ; Pancreatic Neoplasms ; diagnostic imaging ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Radionuclide Imaging ; Receptors, Somatostatin ; biosynthesis ; genetics ; Tumor Cells, Cultured

Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; Gastrointestinal Neoplasms ; classification ; epidemiology ; therapy ; Humans ; Indoles ; therapeutic use ; Neuroendocrine Tumors ; classification ; epidemiology ; therapy ; Octreotide ; therapeutic use ; Pancreatic Neoplasms ; classification ; epidemiology ; therapy ; Peptides, Cyclic ; therapeutic use ; Pyrroles ; therapeutic use ; Sirolimus ; analogs & derivatives ; therapeutic use ; Somatostatin ; analogs & derivatives ; therapeutic use

OBJECTIVETo investigate the effects of SOM230, a new somatostatin analogue, on the proliferation of hepatocellular carcinoma (HCC) cell line HepG2 in vitro and in vivo, and explore the mechanism underline the necrosis of tumors.

METHODSMTT, TdT-mediated dUTP nick end labeling assay (TUNEL) and flow cytometric assay were used to measure the effects of SOM230 on the proliferation and apoptosis of HCC HepG2 cells. Nude mice bearing HCC xenografts of the HepG2 cell line were treated with SOM230 (100 microg/kg/d subcutaneously injection) and saline as a control for eight weeks. The mass and percentage of necrotic volume of the HCC xenografts in nude mice were determined. Western blot was used to detect SSTR2 in HCC xenografts. Immunohistochemical method was used to detect the expression sites of SSTR2 and VEGF in HCC xenografts. ELISA was used to detect the levels of TNFalpha.

RESULTSNo proliferation and apoptosis of HepG2 cells were induced by SOM230 in vitro (F = 0.16, P more than 0.05). The percentage of necrotic volume in SOM230 were significantly higher than that of control group (73.4%+/-7.0% vs 30.2%+/-14.0%, t = -8.02, P more than 0.01). SSTR2 was expressed in blood sinus of HCC xenografts in nude mice. There was no significance difference in the level of SSTR2 expression between SOM230 group and saline treated group. VEGF expression in xenografts was down-regulated by SOM230 treatment. SOM230 treatment did not affect the level of TNFalpha in HCC xenografts (t = -0.24, P more than 0.05).

CONCLUSIONSSOM230 can induce massive necrosis of HCC xenografts only after the blockage of blood flow through down-regulation of VEGF mediated by SSTR2.

Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Disease Models, Animal ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Injections, Subcutaneous ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Receptors, Somatostatin ; metabolism ; Somatostatin ; administration & dosage ; analogs & derivatives ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the effect of 99Tcm-HYNIC-TOC imaging in localization of somatostatin receptor-positive tumors.

METHODSForty-four patients were involved in this study, including 22 neuroendocrine tumors, 10 non-neuroendrocrine tumors and 12 benign diseases. All patients were confirmed by histopathologic diagnosis, and had clinical laboratory data, or 1-2 other imaging procedures. Regional, whole body and SPECT/CT (in positive cases) imagings were acquired at 1 and 4 hours after an intravenous injection of 370 MBq 99Tcm-HYNIC-TOC. 99Tcm-HYNIC-TOC imaging was compared with 111In-petetreotide imaging in 4 cases, and with 131I-MIBG imaging in 10 cases. 99Tcm-HYNIC-TOC imaging was performed before and after treatment in 1 non-Hodgkins lymphoma (NHL) patient.

RESULTSThe positive imagings were observed in 19 of 32 cases. The sensitivity, specificity, and accuracy of 99Tcm-HYNIC-TOC imaging for somatostatin receptor-positive tumors are 82.6%, 100%, and 87.5%, respectively. The distribution in vivo of 99Tcm-HYNIC-TOC is similar to that of 111In-petetreotide, and showed high physiological uptake in liver, spleen, and kidneys. 99Tcm-HYNIC-TOC imaging demonstrated intense tumor sites uptake at 1 hour after injection, and revealed the lesions first in 6 patients among the imaging modalities, and more lesions that had not been revealed by 131I-MIBG imaging. Compared with imaging before treatment, 99Tcm-HYNIC-TOC imaging confirmed the tumor regression after treatment in 1NHL.

CONCLUSIONS99Tcm-HYNIC-TOC is promising for the diagnosis and localization of somatostatin receptor-positive tumors.

Adenoma, Chromophobe ; diagnostic imaging ; Adult ; Carcinoma, Medullary ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors ; diagnostic imaging ; metabolism ; Octreotide ; analogs & derivatives ; Organotechnetium Compounds ; Pancreatic Neoplasms ; diagnostic imaging ; Pituitary Neoplasms ; diagnostic imaging ; Receptors, Somatostatin ; metabolism ; Thyroid Neoplasms ; diagnostic imaging ; Tomography, Emission-Computed, Single-Photon

Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Amylases/metabolism ; Animal ; Baclofen/pharmacology ; Baclofen/analogs & derivatives* ; Bicuculline/pharmacology ; Cholecystokinin/metabolism ; Dose-Response Relationship, Drug ; Electric Stimulation ; GABA/pharmacology* ; GABA Antagonists/pharmacology ; Gastrin-Releasing Peptide/metabolism ; Hormones/pharmacology ; In Vitro ; Pancreas/secretion* ; Pancreas/enzymology ; Pancreas/drug effects* ; Rats ; Receptors, GABA-A/metabolism ; Secretin/metabolism ; Somatostatin/pharmacology ; Tetrodotoxin/pharmacology