Higher GABA Concentrations in Fallopian Tube Than in Brain of the Rat

Erdö, Sándor L.; Rosdy, B.; Szporny, L

doi:10.1111/j.1471-4159.1982.tb05368.x

Cited by 86 publications

(31 citation statements)

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“…and peripheral organs. For example, GABA is highly concentrated in rat pancreatic islets (23) and fallopian tube (24) together with the enzyme glutamic acid decarboxylase responsible for biosynthesis. An RT-PCR analysis shows the expression of both GABA B R1 splice variants in rat peripheral organs, in addition to brain, as seen in the present study.…”

Section: Discussionmentioning

confidence: 99%

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Takahata¹,

Takarada²,

Hinoi

et al. 2011

Journal of Biological Chemistry

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The prevailing view is that signaling machineries for the neurotransmitter GABA are also expressed by cells outside the CNS. In cultured murine calvarial osteoblasts, mRNA was constitutively expressed for both subunits 1 and 2 of metabotropic GABA B receptor (GABA B R), along with inhibition by the GABA B R agonist baclofen of cAMP formation, alkaline phosphatase (ALP) activity, and Ca 2؉ accumulation. Moreover, baclofen significantly inhibited the transactivation of receptor activator of nuclear factor-B ligand (RANKL) gene in a manner sensitive to a GABA B R antagonist, in addition to decreasing mRNA expression of bone morphogenetic protein-2 (BMP2), osteocalcin, and osterix. In osteoblastic MC3T3-E1 cells stably transfected with GABA B R1 subunit, significant reductions were seen in ALP activity and Ca 2؉ accumulation, as well as mRNA expression of osteocalcin, osteopontin, and osterix. In cultured calvarial osteoblasts from GABA B R1-null mice exhibiting low bone mineral density in tibia and femur, by contrast, both ALP activity and Ca 2؉ accumulation were significantly increased together with promoted expression of both mRNA and proteins for BMP2 and osterix. No significant change was seen in the number of multinucleated cells stained for tartrate-resistant acid phosphatase during the culture of osteoclasts prepared from GABA B R1-null mice, whereas a significant increase was seen in the number of tartrate-resistant acid phosphatase-positive multinucleated cells in co-culture of osteoclasts with osteoblasts isolated from GABA B R1-null mice. These results suggest that GABA B R is predominantly expressed by osteoblasts to negatively regulate osteoblastogenesis through down-regulation of BMP2 expression toward disturbance of osteoclastogenesis after down-regulation of RANKL expression in mouse bone.In the mammalian CNS, GABA is the major inhibitory amino acid neurotransmitter with two major receptor subtypes categorized into ionotropic and metabotropic receptors on the basis of homologous intracellular signals (1). The ionotropic GABA A receptor is a heteromeric protein complex composed of a number of different receptor subunits, whereas the GABA C R is derived from an assembly between various isoforms of the subunit (2). The metabotropic GABA B R belongs to a superfamily of the seven-transmembrane-domain receptors with high similarity to metabotropic receptors for the central excitatory amino acid neurotransmitter L-glutamic acid (3). The GABA B R couples to adenylyl cyclase through trimeric G-proteins to negatively regulate intracellular cAMP formation, in addition to inhibiting voltage-sensitive Ca 2ϩ channels and activating voltage-sensitive K ϩ channels, respectively. The GABA B R is orchestrated by a heterodimer comprised of members of GABA B R1 and GABA B R2 subunits, neither of which is fully functional when individually expressed. Any GABA B R1 subunits are unable to activate K ϩ channels alone (4), whereas heterodimerization between GABA B R1 and GABA B R2 subunits is required for the orchestration ...

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Section: Discussionmentioning

confidence: 99%

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Takahata¹,

Takarada²,

Hinoi

et al. 2011

Journal of Biological Chemistry

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“…The rat oviduct contains more than twice as much GABA as the whole brain [Erdo et al 1982;Celotti et al 1986]. Extremely high levels of GABA are concentrated in the oviduct mucosa that exceed by ten-fold, those in brain [Murashima and Kato 1986].…”

Section: Introductionmentioning

confidence: 99%

Activation of GABA_AReceptor/Cl⁻Channel and Capacitation in Rat Spermatozoa: HCO₃⁻and Cl⁻are Essential

Jin

Chen

Zhou

et al. 2009

Systems Biology in Reproductive Medicine

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This study was designed to determine whether HCO 3 À and Cl À are required for the activation of the GABA A receptor/Cl À channel (GBRC) by GABA and the subsequent capacitation of rat sperm. Spermatozoa from adult Sprague Dawley rats were incubated in four different media: modified complete rat fertilization medium (mRFM), Cl À -deficient (Cl À -DF) mRFM, HCO 3 À -DF mRFM, andCl À -DF HCO 3 À -DF mRFM, with or without GBRC agonists (GABA and progesterone) or GBRC antagonists (bicuculline and picrotoxin) for 0-6 h under capacitating conditions. Sperm capacitation and hyperactivation were assessed by chlortetracycline staining and computer-assisted sperm analysis, respectively. The results showed that GABA added to the mRFM accelerated capacitation and hyperactivation, followed by increase in the acrosome reaction, reaching maximum value after 5 h. Progesterone also accelerated sperm capacitation and hyperactivation. Bicuculline and picrotoxin, antagonists of GABA, blocked the effects of both GABA and progesterone acceleration of sperm capacitation and hyperactivation. Sperm capacitation required both Cl À and HCO 3 À . These results indicate that activation of GBRC may contribute to sperm capacitation and hyperactivation, and that both HCO 3 À and Cl À are essential. This is the first report of a close relationship between HCO 3 À /Cl À transport and the activation of GBRC in rat sperm capacitation and hyperactivation.

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“…GABAA receptor is expressed in human sperm [8,9]. It is interesting to note that rat oviduct contains more than twice the amount of GABA than the brain [10]. Moreover, GABA A receptor mediates progesterone-induced acrosome reaction (AR), an exocytotic event…”

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confidence: 99%

Identification of GABABR2 in Rat Testis and Sperm

Zhang

Yan

et al. 2003

Journal of Reproduction and Development

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Abstract. GABA is capable of mimicking and potentiating the action of progesterone in initiating the acrosome reaction (AR) of mammalian sperm. The GABA-initiated AR is mediated by GABA AR; whereas GABABR1 protein found in rat testis and sperm tends to modify this process. Moreover, the occurrence of GABABR2, a subunit essential for the formation of a functionally active GABABR, in rat testis and sperm has not been established. In the present study, rat testis and sperm were analyzed for the presence of GABABR2 transcript and protein by RT-PCR, Northern blot, Western blot and an indirect immunofluorescence technique. Northern blot shows that the transcript of testis GABABR2 is shorter (~3.0 Kb) than that of the brain (~5.6 Kb). The full length testis GABABR2 cDNA was prepared by RACE-PCR and found to be shorter by 2.2 Kb in the segment at the extreme terminus of 3'UTR of rat brain GABABR2 but, the sequences corresponding to the open reading frame and 5'-UTR of rat testis GABABR2 were found to be identical to those of rat brain. GABABR2 protein isolated from rat epididymal sperm was slighter larger than those of rat testis and brain. It was principally localized in the acrosome region of the head of rat sperm by an indirect immunofluorescence technique. The present results establish that GABABR2 protein is produced in rat testis and sperm and may play a role in GABA triggering of AR. Key words: GABABR2, Testis, Sperm (J. Reprod. Dev. 49: [397][398][399][400][401][402] 2003) -Aminobutyric acid (G ABA) is t he mos t abundant inhibitory neurotransmitter in the vertebrate central nervous system (CNS). Its effects are mediated through two ligand-gated channels ( G A B A A a n d G A B A C r e c e p t o r s ) , a n d a m e t a bo t r o pi c G p ro te in -c o up led r e ce pt o r , GABABR. This species of the receptor acts through G proteins by regulating potassium and calcium channels [1]. The first GABAB receptor cDNA (termed GABABR1) was isolated first from rat brain with a high affinity radio-ligand [2]. After the cloning the GABA B R1, another subunit of GABA B receptor, GABA B R2, was identified [3][4][5]. Several l i n e s o f e v i d e n c e d e m o n s tr a t e d th a t t h e heterodimerization of GABABR1 and GABABR2 is a requirement for the formation of a functional GABAB receptor [3][4][5][6]. GABABR1 and GABABR2 form a heterodimer by a linkage involving the interaction at the C-terminal tails [6].A GABAergic system also occurs in several peripheral tissues [7] e.g. GABAA receptor is expressed in human sperm [8,9]. It is interesting to note that rat oviduct contains more than twice the amount of GABA than the brain [10]. Moreover, GABA A receptor mediates progesterone-induced acrosome reaction (AR), an exocytotic event

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Higher GABA Concentrations in Fallopian Tube Than in Brain of the Rat

Cited by 86 publications

References 6 publications

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Activation of GABA_AReceptor/Cl⁻Channel and Capacitation in Rat Spermatozoa: HCO₃⁻and Cl⁻are Essential

Identification of GABABR2 in Rat Testis and Sperm

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Higher GABA Concentrations in Fallopian Tube Than in Brain of the Rat

Cited by 86 publications

References 6 publications

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Osteoblastic γ-Aminobutyric Acid, Type B Receptors Negatively Regulate Osteoblastogenesis toward Disturbance of Osteoclastogenesis Mediated by Receptor Activator of Nuclear Factor κB Ligand in Mouse Bone

Activation of GABAAReceptor/Cl−Channel and Capacitation in Rat Spermatozoa: HCO3−and Cl−are Essential

Identification of GABABR2 in Rat Testis and Sperm

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Activation of GABA_AReceptor/Cl⁻Channel and Capacitation in Rat Spermatozoa: HCO₃⁻and Cl⁻are Essential