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gamma-Aminobutyric acid type B (GABA(B)) receptors mediate the metabotropic actions of the inhibitory neurotransmitter GABA. These seven-transmembrane receptors are known to signal primarily through activation of G proteins to modulate the action of ion channels or second messengers. The functional GABA(B) receptor is made up of a heterodimer consisting of(More)
In recombinant cell lines, functional GABA(B) receptors are only formed by the heterodimerisation between two related G-protein coupled receptor proteins GABA(B)R1 (GBR1) and GABA(B)R2 (GBR2), whilst the individual GBR1 or GBR2 do not produce fully functional receptors. To determine whether the heterodimerisation occurs in vivo, novel polyclonal antibodies(More)
Following the recent discovery that GABA(B) receptors expressed in cell lines are only functional when both GABA(B1) and GABA(B2) are expressed, the present study reports on the development of polyclonal antisera specific for carboxyl-terminal portions of the two related GABA(B) receptor components respectively. Western blotting indicated the specificity of(More)
A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X(7) antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X(7) in the etiology of pain is also(More)
It has been postulated that the G protein-coupled receptor, GPR55, is a third cannabinoid receptor. Given that the ligands at the CB(1) and CB(2) receptors are effective analgesic and anti-inflammatory agents, the role of GPR55 in hyperalgesia associated with inflammatory and neuropathic pain has been investigated. As there are no well-validated GPR55 tool(More)
The presence of metabotropic receptors for GABA, GABAB, on primary afferent terminals in mammalian spinal cord has been previously reported. In this study we provide further evidence to support this in the rat and show that the GABAB receptor subunits GABAB1 and GABAB2 mRNA and the corresponding subunit proteins are present in the spinal cord and dorsal(More)
Several studies have implicated a potential role for histamine H(3) receptors in pain processing, although the data are somewhat conflicting. In the present study we investigated the effects of the novel potent and highly selective H(3) receptor antagonists GSK189254(More)
UNLABELLED The role of specific nicotinic receptor (nAChR) subtypes in antinociception has not been fully elucidated because of the lack, until recently, of selective tool compounds. (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiopene-2-carboxamide) (compound B) is reported to be an agonist selective for the alpha(7)nAChR and in the present study was(More)
The molecular nature of the metabotropic GABA(B) receptor was for some time a mystery, however it was recently discovered that two related G-protein-coupled receptors have to heterodimerize to form the functional GABA(B) receptor at the cell surface. This review discusses the most recent findings in the rapidly expanding field of GABA(B) receptor research,(More)
The GABA(B) receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABA(B)R1 and GABA(B)R2. In this study, the cellular distribution of the GABA(B)R1 and GABA(B)R2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The(More)