著者

麻川 武雄 榎本 恵一 高野 正子

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学雑誌 (ISSN:00155691)

巻号頁・発行日

vol.101, no.2, pp.59-68, 1993

被引用文献数

1

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Adenylate cyclase is a key enzyme that couples with both the stimulatory and inhibitory G proteins (G<SUB>s</SUB> and G<SUB>i</SUB>). The cyclase has been purified and shown to be a glycoprotein of molecular weight 115, 000-180, 000. Cloning of cDNAs for adenylate cyclase showed that the cyclase is a member of a large family consisting of a variety of subtypes of the enzyme. These subtypes show different responses to calmodulin and G protein &beta;&gamma; subunits, and their distributions in tissues and organs are also different. This suggests that each subtype is involved in a particular physiological function. The general structure of adenylate cyclase is composed of two cytoplasmic domains and two membrane-spanning domains, each of which contains 6 transmembrane spans (12 spans in a molecule). The amino acid sequence of each cytoplasmic domain, which is thought to contain a nucleotide (ATP) binding site, is well-conserved among the various subtypes. This review also focuses on the regulation of adenylate cyclase activity by G protein subunits, particularly on several models for adenylate cyclase inhibition by G<SUB>i</SUB>. As one of these mechanisms, direct inhibition of adenylate cyclase by the &beta;&gamma; subunits recently demonstrated by us will be discussed.