title: Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.
abstract: The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Kang
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.forename: Chea-Ha
authors.initials: CH
authors.lastname: Kim
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.forename: Ohk-Hyun
authors.initials: OH
authors.lastname: Ryu
authors.forename: Moon-Gi
authors.initials: MG
authors.lastname: Choi
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018079:Receptors, GABA / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D018079:Receptors, GABA; C052329:phaclofen; D001418:Baclofen