Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Türkiye
Tezin Onay Tarihi: 2005
Tezin Dili: İngilizce
Öğrenci: Serpil Apaydın
Danışman: HÜSEYİN AVNİ ÖKTEM
Özet:Effect of lipids on binding characteristics of opioid receptors in membranes prepared from rat brain were studied. Lipid concentrations causing changes in specific binding of [3H]Endomorphin-1 (ProE1), an opioid agonist highly specific to mu-type opioid, [3H]Ile5,6deltorphin II (DIDI), an agonist ligand highly specific to delta type receptor and [3H]Naloxone (Nlx), a universal opioid receptor antagonist were determined. Inhibition of [3H]ProE1, [3H]DIDI and [3H]Nlx specific binding was also examined by homologous displacement experiments in the presence and absence of lipids. In order to understand whether the changes occurring in the specific binding is due to changes in equilibrium dissociation constant (KD) or maximum number of binding sites (Bmax), the equilibrium binding experiments were performed. Arachidonic acid (AA) inhibited binding of both agonist and antagonist ligand in a dose dependent manner with IC50 values of 0.15, 0.1, and 0.6 mM for [3H]ProE1, [3H]DIDI and [3H]Nlx, respectively. Kd values were not affected while Bmax values decreased 38 % and 76 % for mu, and delta receptor subtypes, respectively. For [3H]Nlx, Bmax values decreased 20 and 56 % in the absence and presence of 100 mM NaCl, respectively. Cholesteryl hemisuccinate (CHS) enhances (100 % of control) ligand binding at mu-sites however no effect was encountered at delta sites. Furthermore, CHS also enhances (50 % of control) the binding of antagonist ligand in the absence of NaCl. Bmax values were increased by 70 % for mu sites and 40% for antagonist ligand binding site. Under similar conditions Kd values were not affected. Phosphatidic acid (PA) and phosphatidylcholine (PC) exhibited negligible effect on ligand binding. PA decreased specific binding of ProE1 and DIDI by 16 and 10 %, respectively. Specific binding of antagonist ligand Nlx decreased 11 % in the presence of NaCl whereas in the