Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-voltage-activated T-type Ca2+ channels are present in most excitable tissues including the heart (mainly pacemaker cells), smooth muscle, central and peripheral nervous systems, and endocrine tissues, but also in non-excitable cells, such as osteoblasts, fibroblasts, glial cells, etc. Although they comprise a slightly heterogeneous population, these channels share many defining characteristics: small conductance (< 10 pS), similar Ca2+ and Ba2+ permeabilities, slow deactivation, and a voltage-dependent inactivation rate. In addition, activation at low voltages, rapid inactivation, and blockade by Ni2+ are classical properties of T-type Ca2+ channels, which are less specific. T-type Ca2+ channels are weakly blocked by standard Ca2+ antagonists. Pharmacological blockers are scarce and often lack specificity and/or potency. The physiological modulation of T-type Ca2+ currents is complex: they are enhanced by endothelin-1, angiotensin II (AT1-receptor), ATP, and isoproterenol (cAMP-independent), but are reduced by angiotensin II (AT2-receptor), somatostatin and atrial natriuretic peptide. Norepinephrine enhances these currents in some cells but decreases them in others. T-type Ca2+ currents have many known or suggested physiological and pathophysiological roles in growth (protein synthesis, cell differentiation, and proliferation), neuronal firing regulation, some aspects of genetic hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac rhythm (normal and abnormal), and atherosclerosis. Mibefradil is a new Ca2+ antagonist that is effective in hypertension and angina pectoris. Its favorable pharmacological profile and limited side effects appear to be related to selective block of T-type Ca2+ channels: mibefradil reduces vascular resistance and heart rate without negative inotropy or neurohormonal stimulation, and it also has significant antiproliferative actions.
Cardiovasc Drugs Ther 1997 Dec
PMID:T-type Ca2+ channels and pharmacological blockade: potential pathophysiological relevance. 951 67

Carcinoid syndrome originates from metastatic carcinoid tumors localized in the gastrointestinal system, pancreas, biliary vessels, bronchi, ovaries, and testes; it is characterized by flushing, telangiectasias, diarrhea, bronchoconstriction, and fibrous endocardial plaques in the heart. Cardiac involvement is detected by echocardiography in over 50% of patients with this syndrome. Right-sided valvular heart disease occurs frequently in patients with carcinoid syndrome, involving most commonly the tricuspid and pulmonary valves. Involvement of the left-sided valves rarely occurs. Medical therapy for carcinoid heart disease includes digitalis and diuretics for congestive heart failure symptoms; the effects of carcinoid syndrome can be treated with the use of somatostatin analogues. Conventional chemotherapy has been of little beneficial value, with response rates of only 10% to 30%. The use of octreotide, a long-acting and potent somatostatin analogue, is a major advance in the management of carcinoid tumors. In addition to providing effective symptom relief in malignant carcinoid syndrome, octreotide can also be used for diagnostic purposes. Despite its expense, octreotide is the current agent of choice for the treatment of this condition. Analogues with different receptor specificities and pharmacokinetics hold promise for the future. Valve surgery is the only definitive treatment for intractable right-sided heart failure. Although cardiac surgery carries high perioperative mortality, marked symptomatic improvement occurs in survivors. Surgical intervention therefore should be considered in the appropriate patients when cardiac symptoms become severe. Balloon valvulotomy in patients with severe pulmonary artery stenosis often results in palliation of symptoms; however, surgery still is required often in these patients.
Curr Treat Options Cardiovasc Med 2000 Oct
PMID:Carcinoid Heart Disease. 1109 44

Of the three major functional categories of cardiomyopathies (dilated, hypertrophic, and restrictive), the restrictive cardiomyopathies (RCMs) are the least common in the Western world, but unfortunately often are associated with the greatest morbidity and mortality. Infiltrative disease of the myocardium (often caused by amyloidosis) is a common cause of RCMs and has a significantly lower long-term survival rate when compared to cardiomyopathies of various other causes. Treatment of the RCM is, in general, difficult and often ineffective. Because of the abnormalities of diastolic filling that are characteristic of this condition, general measures to reduce venous and systemic congestion such as with the use of diuretics, are desirable but often result in an attendant reduction in stroke volume and cardiac output. Digoxin, calcium channel blocking drugs, and beta-adrenergic blocking agents are of limited value, although they may be used with benefit to control the heart rate response in the subgroup of patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors are generally ineffective in RCM. Targeted therapy directed against specific causal entities (such as the use of somatostatin analogues in carcinoid syndrome or iron chelation with desferrioxamine in hemochromatosis) may be more effective than simple symptomatic therapy. Differentiation of RCM from constrictive pericarditis is crucial, since constriction may be treated effectively by surgical removal of the thickened pericardium. A limited number of patients appear to have benefited from novel treatment strategies, such as autologous stem cell transplant in amyloidosis, balloon valvuloplasty of stenotic tricuspid or pulmonary valves in cardiac carcinoid syndrome, and cardiac transplantation. Truly effective therapy for RCM is generally lacking, and the best chance for optimizing the clinical outcome is early detection and aggressive medical treatment in an attempt to maintain the highest possible level of patient function for as long as possible.
Curr Treat Options Cardiovasc Med 2000 Oct
PMID:Restrictive Cardiomyopathy. 1109 47

Two patients with a radically operated well differentiated neuroendocrine carcinoma (WDNC) of the lung who developed a carcinoid syndrome due to metastatic spread of the tumor are reported. Treatment with somatostatin analogue octreotide was administered to both patients following their refusal of a standard chemotherapic regimen. Prompt resolution of the carcinoid syndrome was observed in both following octreotide treatment and both patients are alive and well after more than four years without evidence of further progression of the tumor. It is suggested that octreotide should be considered as an effective therapy in WDNC for the control of the disease and associated paraneoplastic syndromes.
J Cardiovasc Surg (Torino) 2000 Oct
PMID:Long-term survival of patients treated with octreotide for metastatic well differentiated neuroendocrine carcinoma of the lung. 1114 47

Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial myocardium. Less is known about the effects of somatostatin-14 in ventricular myocardium. The direct contractile effects of somatostatin-14 were assessed using ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence of the beta-adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor of the transient outward current (Ito), 4-aminopyridine (500 microM). Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50 = 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine (500 microM), somatostatin-14 stimulated a positive contractile response (EC50 = 118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate that somatostatin-14 exerts dual effects directly in rat ventricular cardiomyocytes: (1) a negative contractile effect, observed in the presence of isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously unreported and very potent positive contractile effect, unmasked by 4-aminopyridine (500 microM), coupled to the influx of calcium ions via L-type calcium channels. The greater potency of somatostatin-14 for producing the positive contractile effect indicates that the peptide may exert a predominantly stimulatory influence on the resting contractility of ventricular myocardium in vivo, whereas the negative contractile effect, observed at much higher concentrations, could indicate that localized elevations in the concentration of the peptide may serve as a negative regulatory influence to limit the detrimental effects of excessive stimulation of cardiomyocyte contractility.
J Cardiovasc Pharmacol 2001 Mar
PMID:Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes. 1124 23

Intrapericardial teratoma was diagnosed in a nine-year-old male infant with a three-month history of labored breathing and cough. The tumor was completely resected and found to be a mature teratoma, containing pancreatic tissue and producing insulin. A few glucagon and somatostatin containing cells were also present in the periphery of the islets. Postoperative course was uneventful. This is to our knowledge, the first report of an intrapericardial teratoma with such endocrine activity.
J Cardiovasc Surg (Torino) 2001 Dec
PMID:An intrapericardial teratoma with endocrine function. 1169 46

Persistent pleural effusion developed in an 81-year-old man with acute pulmonary edema due to myocardial dysfunction. Daily chest tube drainage was 1,000 to 1,400 mL. Despite total parenteral nutrition and albumin supplementation, drainage did not decrease. However, continuous infusion of a somatostatin analog was effective in controlling the effusion.
Asian Cardiovasc Thorac Ann 2003 Mar
PMID:Conservative management of persistent pleural effusion using somatostatin. 1269 28

Somatostatin analogues have been shown to inhibit smooth muscle cell proliferation after local administration in vivo in animal models and in vitro using human coronary smooth muscle cell cultures. However, the optimal dosage for attaining effective site-specific administration remains undefined. This study was performed to determine the required theoretical dose of the somatostatin analogue, octreotide, to be delivered site specifically, for prevention of restenosis after coronary angioplasty in humans using a previously described methodology to determine regional pharmacokinetics of site-specific intracoronary administrated compounds. In 7 patients, 111In-octreotide, a gamma-labeled somatostatin analogue, was infused post angioplasty at the site of dilatation via a coil-balloon and quantified using a radio-isotopic technique. Efficiency of delivery ranged from 0.1% to 2.7% of the total infused dose of 0.18 microg, corresponding to a mean peak delivered amount of 1.8 +/- 1.9 ng. Total locally bioavailable 111In-octreotide reached 2.28 +/- 2.15 ng h. Based on current in vitro bioavailability and peak concentration data to inhibit proliferation and thymidine incorporation in human coronary smooth muscle cells, a 4000x higher averaged dose (approximately 700 microg) should be infused site specifically to obtain a biologic efficacy in 50% of the treated patients (ED50). Quantification of regional pharmacokinetics enables the determination of a theoretical site-specific dose for achieving appropriate bioavailability above the therapeutic threshold concentration for smooth muscle cell inhibition. This approach is proposed for the determination of the appropriate site-specific coronary infusion dose for the inhibition of restenosis after balloon angioplasty.
J Cardiovasc Pharmacol 2004 Jan
PMID:Site-specific intracoronary delivery of octreotide in humans: a pharmacokinetic study to determine dose-efficacy in restenosis prevention. 1466 79

The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning. A representative sampling of the wide array of radiopharmaceuticals developed specifically for radionuclide imaging of atherosclerosis, that have been approved for clinical use and those in pre-clinical trials, have been reviewed in this article. The presence of an inflammatory stimulus increases expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on monocytes and macrophages, and somatostatin receptors on T lymphocytes. Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to CCR-2 and can be used to detect subacute and chronic inflammatory lesions. Similarly, radiolabeled octreotide or depreotide can be used to detect activated T lymphocytes which may identify the vulnerable plaque. Animal models indicate that (99m)Tc-annexin V, (125)I-MCP-1 and [(18)F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of alpha(v)beta(3) integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and alpha(v)beta(3) integrin is minimally expressed on smooth muscle cells and is not expressed on quiescent epithelial cells. Radiolabeled high-affinity peptides can be used to target the alpha(v)beta(3) integrin and visualize areas of vascular damage. Advances in technology such as the micro-single photon emission computed tomography (microSPECT) have the potential to overcome the drawbacks of older CT and MRI methodologies, such as lack of biologically relevant ligands and compatible blood pool contrast agents for imaging. Despite these advances in imaging technology, the small size of atheromatous lesions makes it difficult to detect using external imaging techniques. Therefore, recently there has been renewed interest in the use of intravascular catheter-based radiation detectors.
Am J Cardiovasc Drugs 2002
PMID:Development of radiocontrast agents for vascular imaging: progress to date. 1472 51

We tested the hypothesis that octreotide, a somatostatin analogue, can mimic ischemic preconditioning (PC) to provide cardioprotection against myocardial infarction. An ischemia-reperfusion model of adult Wistar rats was used. Infarct size was expressed as a percentage of the area at risk under different treatment protocols. Octreotide PC (35 microg/Kg 20 minutes before ischemia-reperfusion) significantly decreased infarct size (18 +/- 4%) versus control (60 +/- 7%). The somatostatin receptor antagonist cyclo-somatostatin (0.5 mg/Kg) could blunt the above cardioprotection. Administration of either chelerythrine (a protein kinase C inhibitor, 2 mg/Kg) or genistein (a tyrosine kinase inhibitor, 5 mg/Kg) could also block octreotide PC (54 +/- 7% and 58 +/- 6%, respectively). Pretreatment with the mitochondrial ATP-sensitive potassium channel antagonist 5-hydroxydecanoic acid (5-HD) and the sarcolemmal ATP-sensitive potassium channel antagonist glibenclamide could abolish the effects of octreotide PC (54 +/- 6% and 52 +/- 6%). Chelerythrine, however, had no effect on octreotide PC. In conclusion, the present study demonstrates that octreotide can mimic ischemic PC to reduce infarct size. Acute effects of octreotide PC involve the activation of protein kinase C, tyrosine kinase C, and mitochondrial ATP-sensitive potassium channels, but not systemic IGF-I activation.
J Cardiovasc Pharmacol 2005 Apr
PMID:Somatostatin analogue mimics acute ischemic preconditioning in a rat model of myocardial infarction. 1577 21


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