International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Prof Pyung-Lim Han
Ewha Womans University
Ewha Institute of Neuroscience
Ewha Womans University School of Medicine
70 Jongno-6-Ga, Jongno-Gu
110-783
Republic of Korea

Co-Authors: 1) Lee KW, 1) Hong JH 1) Choi IY, 2) Che Y, 2) Lee JK, 2) Yang SD, 3) Song CW, 3) Han SS, 4) Shin HS
Institutions: 1)Department of Neuroscience and EIN, Ewha Womans University School of Medicine, 2)Department of Anatomy, Inha University School of Medicine, 3)Toxicology Research Group, KRICT, 4)National CRI Center for Calcium and Learning, KIST

The dopamine receptor subtypes, D1 and D2, are co-localized in the striatum, and have been envisioned to stimulate or inhibit adenylyl cyclases (ACs) to produce subtype specific physiological and pharmacological responses. Adenosine receptor (A2a) and muscarinic acetylcholine receptor (M4) are also coupled to AC, expressed abundantly in the striatum, and interact with dopaminergic systems synergistically or antagonistically at various levels. However, the in vivo integrity of the effector system of these receptors is poorly determined. To specify the in vivo role of the type 5 adenylyl cyclase (AC5), an AC that is preferentially expressed in the striatum, we generated mice deficient for the AC5 gene. Biochemical analyses with AC5 deficient mice indicated that AC5 was necessary not only for Gs-coupled receptors, D1 and A2a, but also for Gi-coupled receptors, D2 and M4. In the absence of AC5, the D1, A2a M4 receptors were able to constitute a functional receptor-AC system with other AC present in the striatum, whereas the D2 receptors were completely impaired. These results suggest that the synergistic or antagonistic interaction among D1, D2, A2a, and M4 receptor systems in the brain could take place by integrating signals from these neurotransmitter receptors at the level of AC5.