Function and distribution of GABAB receptors

GABA（γ-氨基丁酸）是中枢神经系统中的主要抑制性神经递质，也存在于几种外周组织中，在肌肉收缩或激素分泌的调节中发挥功能作用。GABA的受体可分为两个主要亚型，亲离子型GABAA和亲代谢型GABAB受体。GABAA受体是几种中枢活性药物（包括巴比妥类和苯二氮卓类）的靶点，并对拮抗剂荷包牡丹碱有反应。GABAA受体的激活导致氯离子通道的开放和突触后细胞的超极化。GABAB受体在操作上被巴氯芬选择性激活，对荷包牡丹碱缺乏敏感性，并通过G蛋白抑制腺苷酸环化酶活性，刺激磷脂酶A2，激活K+通道，阻断电压依赖性Ca 2+通道，调节肌醇磷脂水解。Re ...更多信息 本研究发现，GABAB受体激活了在爪蟾卵母细胞中异源表达的Kir3.1和Kir3.2，并在筛选大鼠小脑cDNA文库时发现了两个新的代谢型γ-氨基丁酸受体（GABABR 1）剪接体，命名为GABABR 1C和GABABR 1d。GABABR 1c具有与GABABR 1同种型成员GABABR 1b相同的氨基酸序列，以及在GABABR 1b的第五跨膜区产生额外的31个氨基酸序列的额外93-bp插入。因此，GABABR 1c可能在第二胞外环和第五跨膜区中具有结构变异。GABABR 1d也具有与GABABR 1b相同的氨基酸序列和在羧基末端产生不同氨基酸序列的566 bp的额外插入。逆转录聚合酶链反应分析表明，在各种大鼠组织中GABABR 1c mRNA的普遍表达和GABABR 1d mRNA在前脑，小脑，眼睛，肾脏和膀胱。GABABR 1亚型不仅在中枢神经系统中起作用，而且在各种外周组织中也起作用。少

GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system and is also present in several peripheral tissues, where it could have a functional role in the regulation of muscle contraction or hormonal secretion. The receptors for GABA are pharmacologically classified into two major subtypes, ionotropic GABAA and metabotropic GABAB receptors. The GABAA receptor is the target of several centrally active drugs, including barbiturates and benzodiazepines, and responds to the antagonist bicuculline. Activation of the GABAA receptor results in opening of a chloride channel and hyperpolarization of postsynaptic cells. The GABAB receptor is operationally defined by selective activation by baclofen and thc lack of sensitivity towards bicuculline, and functions through G proteins to inhibit adenylyl cyclase activity, stimulate phospholipase A2, activate K+ channels, inactivate voltage-dependent Ca2+ channels, and modulate inositol phospholipid hydrolysis. Re … More cently, we have suggested that GABAB receptors activate Kir3.1 and Kir3.2 heterologously expressed in Xenopus oocytes with poly(A)+ RNA derived from rat cerebellum.We have identified two novel splice variants of the metabotropic γ-aminobutyric acid receptor (GABABR1), designated GABABR1C and GABABR1d, when screening a rat cerebellum cDNA library. GABABR1c has an amino acid sequence identical to GABABR1b, a member of GABABR1 isoforms, and an additional 93-bp insertion that generates an additional 31-amino-acid sequence in the fifth transmembrane region of GABABR1b. Thus, GABABR1c may have a structural variation in the second extracellular loop and fifth transmembrane region. GABABR1d also has an amino acid sequence identical to GABABR1b and an additional insertion of 566 bp that generates a divergent amino acid sequence in thc carboxylterminal end. Reverse-transcription polymerase chain reaction analysis showed that in various rat tissues GABABR1c mRNA was ubiquitously expressed and GABABR1d mRNA in forebrain, cerebellum, eye, kidney, and urinary bladder. GABABR1 isoforms may function not only in the central nervous system but also in various peripheral tissues. Less