Co-application of the GABA B receptor agonist, baclofen, and the mGlu receptor agonist, L-CCG-I, facilitates [ 3 H]GABA
- PDF / 339,100 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 92 Downloads / 164 Views
TRANSLATIONAL NEUROSCIENCES - ORIGINAL ARTICLE
Co-application of the GABAB receptor agonist, baclofen, and the mGlu receptor agonist, L-CCG-I, facilitates [3H]GABA release from rat cortical nerve endings Irene A. Samengo • Valerio Scotti Maria Martire
•
Received: 10 April 2013 / Accepted: 19 June 2013 Ó Springer-Verlag Wien 2013
Abstract Interaction between different transmitter receptor systems is an emerging feature of neurotransmission at central synapses. G protein-coupled receptors’ ability to form dimers or larger hetero-oligomers probably serves to facilitate the integration of diverse signals within the cell. We found that, in nerve terminals isolated from the cerebral cortices of rats, co-application of the GABAB agonist, baclofen, and of the non-selective mGlu agonist, L-CCG-I, potentiates the basal and depolarization-evoked release of [3H]GABA via a mechanism that involves mobilization of intracellular Ca2? ions. The effect of L-CCG-I ? baclofen was abolished by the phospholipase C inhibitor U73122, reduced by Xestospongin C (an IP3 receptor blocker), and blocked by 2-APB, an IP3 receptor antagonist. Pretreatment of the synaptosomes with the lipid-soluble Ca2? chelator BAPTA-AM also inhibited the effects of L-CCGI ? baclofen. Subtype-selective non-competitive group I mGlu receptor antagonists, MPEP and CPCCOEt, had no effect on the release enhancement produced by baclofen ? L-CCG-I. The enhancement was reversed by the GABAB receptor antagonist, CGP54626, and by the group I/group II mGlu receptor antagonist (R,S)-MCPG. The GABA release-enhancing effects of L-CCG-I ? baclofen in our model might reflect the presence on cortical nerve endings of GABAB/group I mGlu receptor heteromers with pharmacological properties distinct from those of the component receptors. Activation of these heteromeric receptors might modify the function of the GABAB receptor in such a way that it facilitates GABAergic
I. A. Samengo V. Scotti M. Martire (&) Institute of Pharmacology, Faculty of Medicine, Catholic University of Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy e-mail: [email protected]
transmission, an effect that might be useful under conditions of excessive glutamatergic activity. Keywords GABAB and mGlu receptors Baclofen L-CCG-I GABA release Synaptosomes Cerebral cortex
Introduction A rapidly expanding body of evidence indicates that most, if not all, G protein-coupled receptors (GPCRs) are present at the plasma membrane level as dimeric complexes with distinct pharmacological and functional properties (Fredholm et al. 2007; Gurevich and Gurevich 2008; Milligan 2009). Hetero-dimers with properties that are not shared by their respective homomers have also been reported (Milligan 2006; Ferre´ et al. 2009). In general, these properties have been observed only in heterologous expression systems, but data consistent with heteromultimeric GPCR complexes in native tissues have also been reported. Class C GPCRs represent an interesting model for studying the role of oligomerization in receptor fu
Data Loading...
