Nucleotide sequence analysis of the binding site on the inositol 1,4,5-trisphosphate type-1 receptor in bipolar disorder — a negative study

Fujimaki, Koichiro; Morinobu, Shigeru; Takahashi, Jun; Yamawaki, Shigeto; Kato, Nobumasa; Kanno, Muneaki; Okuyama, Naoyuki; Kawakatsu, Shinobu; Otani, Koichi; Kusumi, Ichiro; Koyama, Tsukasa

« Previous Next »Journal of Affective Disorders
Volume 65, Issue 2 , Pages 139-143, July 2001

Nucleotide sequence analysis of the binding site on the inositol 1,4,5-trisphosphate type-1 receptor in bipolar disorder — a negative study

Koichiro Fujimaki
- Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan
Shigeru Morinobu
- Department of Psychiatry and Neurosciences, Hiroshima University, School of Medicine, Hiroshima, Japan
- Corresponding author. Tel.: +81-82-257-5206; fax: +81-82-257-5209
Jun Takahashi
- Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan
Shigeto Yamawaki
- Department of Psychiatry and Neurosciences, Hiroshima University, School of Medicine, Hiroshima, Japan
Nobumasa Kato
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Muneaki Kanno
- Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan
Naoyuki Okuyama
- Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan
Shinobu Kawakatsu
- Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan
Koichi Otani
- Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan
Ichiro Kusumi
- Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan
Tsukasa Koyama
- Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan

Received 16 February 2000; accepted 2 June 2000.

Abstract

Pharmacological studies of bipolar disorder suggest that dysfunction of calcium mobilization via phosphatidylinositol-mediated transduction may be involved in its pathogenesis. The present study tests the hypothesis that dysfunction of calcium mobilization in bipolar disorder is due to the mutation of the nucleotide sequence in the FKBP12 binding site on the inositol 1,4,5-trisphosphate type-1 receptor (IP₃R1). Nucleotide sequence analysis of the FKBP12 binding site on IP₃R1 was performed using reverse transcription-polymerase chain reaction and DNA sequencing. The nucleotide sequence in this region was preserved in all subjects. This finding suggests that IP₃R1 dysfunction through the FKBP12 binding site is not involved in the pathogenesis of bipolar disorder.

Keywords: Bipolar disorder, Inositol 1,4,5-trisphosphate receptor, Calcium, Calcineurin, FKBP-12