Kobe Gakuin University is a private, co-educational university located on the western edge of the city of Kobe, in Hyōgo Prefecture in Japan. It was founded in 1966 and overlooks the city of Akashi, the Akashi Straits and the Akashi Kaikyo Bridge - the longest suspension bridge in the world. The university has three campuses in Kobe. These are located near Akashi, near Nagata and on Port Island. Wikipedia.
Takano M.,Kobe Gakuin University |
Matsuyama S.,Himeji Dokkyo University
European Journal of Pharmacology | Year: 2014
Bradykinin is a vasoactive peptide that participates in numerous inflammatory processes, vasodilation, and cell growth/survival; it mainly acts through two receptor subtypes, bradykinin B1 and bradykinin B 2 receptors, which are G protein-coupled receptor (GPCR) family members. Details on ubiquitin-dependent degradation via the lysosome and/or proteasome, and the recycling process that directs bradykinin B2 receptor to the cell surface after agonist-induced endocytosis remain unclear; nevertheless, intracellular localization and internalization of GPCRs following stimulation by ligands are well known. Evidence concerning the nuclear localization and functions of GPCRs has been accumulating. The bradykinin B 2 receptor has been shown to localize in the nucleus and suggested to function as a transcriptional regulator of specific genes. The transfer of membrane GPCRs (regardless of liganding), including the bradykinin B2 receptor to the nucleus can be attributed to the presence of a peptide sequence referred to as the nuclear localization signal (NLS). More recently, we found that nuclear bradykinin B2 receptors form heterodimers with the nuclear lamina protein, lamin C. The function of heterodimerization of the bradykinin B2 receptor with lamin C is still unclear. However, nuclear proteins lamin A/C are involved in a variety of diseases. Although further studies are required to elucidate the precise functions and mechanisms of intracellular and nuclear bradykinin B2 receptors, here we discuss the role of lamin A/C in laminopathies and examine the clinical significance of the bradykinin B2 receptor heterodimer. © 2014 Elsevier B.V.
Lazarus L.H.,National Health Research Institute |
Okada Y.,Kobe Gakuin University
Expert Opinion on Therapeutic Patents | Year: 2012
Although endomorphins-1 (EM-1; H-Tyr-Pro-Phe-Trp-NH 2) and -2 (EM-2; H-Tyr-Pro-Phe-Phe-NH 2) are primarily considered agonists for the μ-opioid receptor (MOR), systematic alterations to specific residues provided antagonists and ligands with mixed μ/δ-opioid properties, suitable for application to health-related topics. While the application of endomorphins as antinociceptive agents and numerous biological endpoints were experimentally delineated in laboratory animals and in vitro, clinical use is currently absent. However, structural alterations provide enhanced stability; formation of MOR antagonists or mixed and dual μ/δ-acting ligands could find considerable therapeutic potential. Areas covered: This review attempts to succinctly provide insight on the development and bioactivity of endomorphin analogues during the past decade. Rational design approaches will focus on the engineering of endomorphin agonists, antagonists and mixed ligands for their application as a multi-target ligand. Expert opinion: Aside from alleviating pain, EM analogues open new horizons in the treatment of medical syndromes involving neural reward mechanisms and extraneural regulation effects on homeostasis. Highly selective MOR antagonists may be promising to reduce inflammation, attenuate addiction to drugs and excess consumption of high-caloric food, ameliorate alcoholism, affect the immune system and combat opioid bowel dysfunction. © 2012 Informa UK, Ltd.
Kamei N.,Kobe Gakuin University |
Takeda-Morishita M.,Kobe Gakuin University
Journal of Controlled Release | Year: 2015
Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. © 2014 Elsevier B.V. All rights reserved.
Harada S.,Kobe Gakuin University |
Fujita-Hamabe W.,Kobe Gakuin University |
Tokuyama S.,Kobe Gakuin University
Journal of Pharmacological Sciences | Year: 2012
Stroke is one of the leading causes of death and disability worldwide. It is well known that hyperglycemia and/or diabetes potentially exacerbate the neuronal damage observed following ischemic stroke. Recent reports have shown that hyperglycemia/glucose intolerance may be induced by cerebral ischemic stress, and that normalization of blood glucose levels during the first 48 h of hospitalization appears to confer greater survival outcomes in stroke patients. However, the mechanisms underlying post-ischemic glucose intolerance remain unclear. Here, we review research to date on the mechanisms through which ischemic neuronal damage develops and on the role of post-ischemic glucose intolerance focusing on insulin and adiponectin signaling and communication between the brain and peripheral tissues. The relationship between ischemic neuronal damage and post-ischemic glucose intolerance is also discussed. With respect to therapeutic options, in addition to traditional post-stroke therapies, we also discuss the effect of anti-diabetic drugs and glucose-sensing neuropeptides on the development of the post-ischemic glucose intolerance and neuronal damage. In conclusion, we support the idea for focusing research on the development of post-ischemic glucose intolerance as a new therapeutic target for the stroke patients. © The Japanese Pharmacological Society.
Yamazaki Y.,Kobe Gakuin University |
Harada S.,Kobe Gakuin University |
Tokuyama S.,Kobe Gakuin University
Brain Research | Year: 2012
Post-ischemic hyperglycemia may be one of the triggers of ischemic neuronal damage. However, the detailed mechanisms of this injury process are still unknown. Here, we focused on the involvement of the sodium-glucose transporter (SGLT), which transports glucose together with Na+ ions, and generates inward currents while transporting glucose into cells, resulting in depolarization and increased excitability. The aim of this study was to determine the involvement of the SGLT in the development of cerebral ischemic stress-induced neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Fasting blood glucose (FBG) was measured using the glucose pilot. Neuronal damage was estimated by histological and behavioral analyses. Phlorizin and glucose were administered by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection. Administration of phlorizin (40, 120 or 200 mg/kg, i.p.) significantly and dose-dependently suppressed the elevation of FBG and ischemic neuronal damage. In contrast, phlorizin (10 or 40 μg/mouse, i.c.v.) significantly and dose-dependently suppressed ischemic neuronal damage without reducing the elevation of FBG. Moreover, the development of neuronal damage was significantly and dose-dependently exacerbated following i.c.v. administration of glucose (10 or 25 (w/v)), and its exacerbation was suppressed by i.c.v. administration of phlorizin (40 μg/mouse). These results suggest that cerebral SGLT is activated by post-ischemic hyperglycemia and may be involved in the exacerbation of ischemic neuronal damage. © 2012 Elsevier B.V.