Intrathecal [D-Pen,D-Pen]-enkephalin (DPDPE; a -opioid agonist) has a profound antinociceptive effect in neuropathic pain. Spinal nitric oxide (NO) has been implicated in the analgesic effect of several G protein-coupled receptor agonists. Little, however, is known about the role of spinal NO in the inhibitory effect of DPDPE on spinal dorsal horn neurons. In the present study, we determined th...

Clinically used GPIIb/IIIa blockers are ligand mimetics, and thereby their binding can induce conformational changes of the platelet integrin GPIIb/IIIa. Since the reversibility of these conformational changes may be an important determinant of potential adverse effects of GPIIb/IIIa blockers, we produced a new monoclonal antibody (anti-LIBS-mAb), and by using its binding properties, we investi...

The dicarboxylate, a-ketoglutarate (aKG), has been identified as the most likely physiological anion involved in renal proximal tubule basolateral membrane (BLM) dicarboxylate/organic anion exchange. In the present study, we characterized the uptake of aKG in BLM and brush-border membrane (BBM) vesicles isolated from rat kidney. In both membrane preparations, aKG uptake was Na-dependent, satura...

n-Alcohols exert a dual action on neuronal nicotinic acetylcholine (ACh) receptors with short-chain alcohols exhibiting potentiating action and long-chain alcohols exhibiting inhibitory action. n-Butanol lies at the transition point from potentiation to inhibition. To elucidate the mechanism of dual action of alcohols, the effects of n-butanol on the human 4 2 ACh receptors expressed in the HEK...

The -opioid antagonist naltrindole has been shown to inhibit graft rejection in vivo and suppress allogeneic mixed lymphocyte reaction (MLR) in vitro, similarly to cyclosporin A. We investigated whether this action is mediated by -opioid receptors using both genetic and pharmacological tools. Naltrindole and two related compounds, 7-benzylidene-7-dehydronaltrexone and naltriben, inhibited MLR p...

We have developed a pharmacokinetic-pharmacodynamic strategy based on the operational model of agonism to obtain estimates of apparent affinity and efficacy of N-cyclopentyladenosine (CPA) analogs for the adenosine A1 receptor-mediated in vivo effect on heart rate in the rat. All analogs investigated produced a significant decrease of the heart rate after intravenous infusion. Individual concen...

The N-methyl-D-aspartate (NMDA) receptor antagonist memantine is an approved drug for treatment of Alzheimer’s disease (AD). Other such treatments are cholinesterase inhibitors and nicotinic acetylcholine receptor (nAChR)-sensitizing agents such as galantamine. The present study was designed to test whether memantine exerts any effect on the cholinergic system, in particular the Ca -conducting ...

In the present study, a novel sulfonylthiourea, 1-[[5-[2-(5chloro-o-anisamido)ethyl]-methoxyethoxyphenyl]sulfonyl]-3methylthiourea, sodium salt (HMR 1402), was investigated using in vitro and in vivo systems. HMR 1402 inhibited rilmakaliminduced currents in rat and guinea pig myocytes (IC50 60 and 509 nM, respectively). Hypoxia-induced shortening of action potential duration at 90% repolarizati...

Previous results from our laboratory demonstrated that S(-)nornicotine, a major tobacco alkaloid and an active nicotine metabolite present in the CNS, increases dopamine release from rat striatal slices in a concentration-dependent and calcium-dependent manner. The present study determined if S(-)nornicotine-evoked dopamine release was the result of nicotinic receptor stimulation. Stereoselecti...

Tobacco and alcohol are the most commonly used drugs of abuse and show the most serious comorbidity. The mesolimbic dopamine system contributes significantly to nicotine and ethanol reinforcement, but the underlying cellular signaling mechanisms are poorly understood. Nicotinic acetylcholine (nACh) receptors are highly expressed on ventral tegmental area (VTA) dopamine neurons, with relatively ...