Sodium Regulation of Agonist Binding at Opioid Receptors. I. Effects of Sodium Replacement on Binding at and #{244}-Type Receptors in 731 5c and NG1 08-15 Cells and Cell Membranes

SUMMARY The effects of varying the sodium concentration (at constant ionic strength) on oploid binding at -and #{244}-opioid receptors in 731 5c and NG1 08-1 5 cells has been examined

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Evidence that the σ1 receptor is not directly coupled to G proteins

Sigma (σ) receptors have been implicated in psychosis, cognition, neuroprotection, and locomotion in the central nervous system. The signal transduction mechanisms for σ receptors have not been fully elucidated. In this study, we examined the possible coupling between σ1 receptors and heterotrimeric guanine nucleotide-binding proteins (G proteins) in rodent brain. In σ1 receptor-rich cerebellar membrane preparations, the competitive binding curves of two σ1 agonists, (+)pentazocine and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrro lidinyl)cyclohexylamine (BD737), were unaffected by the addition of 10 μM guanosine-5\u27-O-(γ-thio)-triphosphate (GTPγS). Neither (+)pentazocine (1-100 μM) nor BD737 (0.01-10 μM) stimulated GTPase activities significantly above basal levels in agonist-stimulated GTPase activity assays in cerebellar membranes. Furthermore, when using the method of agonist-stimulated [35S]GTPγS binding as assessed by autoradiography, we did not observe significant stimulation of [35S]GTPγS binding in rat brain sections by either (+)pentazocine or BD737. The above results demonstrate that the σ1 receptor is not likely be directly coupled to G proteins. (C) 2000 Elsevier Science B.V

Acute and Chronic Effects of Nicotine on Serotonin Uptake in Prefrontal Cortex and Hippocampus of Rats

We sought to investigate the effect of nicotine exposure (chronic and acute) on serotonin transporter (SERT) activity in two regions of the brain important for behavioral effects of nicotine. We first looked at the effects of chronic nicotine exposure (0.7 mg/kg nicotine, twice a day for 10 days) on [3H]5-HT uptake in prefrontal cortex (PFC) and hippocampus of rats. A significant increase in [3H]5-HT uptake was observed in synaptosomes prepared from both regions. To rule out the possibility that the increases were due to the last injection given, in a separate set of experiments a single injection of nicotine was administered the evening before sacrifice. No change in uptake occurred in either region, suggesting that the increases in uptake caused by nicotine was an effect of chronic exposure and not to an acute treatment. SERT binding studies, using prefrontocortical or hippocampal membrane preparations, revealed that chronic nicotine exposure significantly increased Bmax which correlated to an increase in SERT density. Lastly, we looked at the short-term effect of nicotine on [3H]5-HT uptake. Rats received a single nicotine injection 15-75 min before sacrifice. PFC synaptosomes displayed a time-dependent increase in uptake, whereas hippocampal synaptosomes showed an increase at only one time point. © 2003 Wiley-Liss, Inc

Binding of σ receptor ligands and their effects on muscarine-induced Ca\u3csup\u3e2+\u3c/sup\u3e changes in SH-SY5Y cells

In human neuroblastoma SH-SY5Y cell preparations, σ1 receptor agonists (+)-pentazocine and 1S,2R-( -)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl) cyclohexylamine (BD737) competed for [3H]haloperidol binding with Ki values of 67 ± 10 and 14 ± 10 nM, respectively. (+)-Pentazocine or BD737 up to 10 μM did not affect basal levels of intracellular Ca2+ concentration ([Ca2+]i) in these cells, but they significantly reduced muscarine-induced [Ca2+]i changes in a dose-related manner. However, the reduction by (+)-pentazocine was not reversed by the σ1 receptor antagonist haloperidol. Further studies showed (+)-pentazocine, BD737 and haloperidol could compete for [3H]quinuclidinyl benzilate binding in SH-SY5Y cells with Ki values of 0.51 ± 0.06, 0.32 ± 0.07 and 4.4 ± 2.3 μM, respectively. Thus, the inhibitory effects on muscarine-induced [Ca2+]i changes by (+)-pentazocine and BD737 in SH-SY5Y cells were likely due to blockade of muscarinic receptors, not due to σ1 receptor activation by these ligands. © 2002 Elsevier Science B.V. All rights reserved

σ‐Receptor Regulation of [\u3csup\u3e3\u3c/sup\u3eH]Arachidonic Acid Release from Rat Neonatal Cerebellar Granule Cells in Culture

Abstract: σ receptors have been identified in many brain areas and are especially abundant in those regions known to be involved in control of movement. σ receptors have been located autoradiographically in the granule cell layer of cerebellum in adult rat brain. In the current study, we identified σ receptors in rat neonatal granule cells in culture using radioligand binding. The tritium labeled form of the putative σ antagonist haloperidol bound with high affinity to membranes prepared from these cells, and ligands selective for σ receptors competed well against [3H]haloperidol binding. The excitatory amino acid N‐methyl‐d‐aspartate and the direct phospholipase A2 activator melittin stimulated the release of [3H]arachidonic acid from cerebellar granule cells. The N‐methyl‐d‐aspartate‐stimulated, but not the melittin‐stimulated, release was inhibited in a concentration‐dependent manner by the σ‐selective agonist (+)‐pentazocine. In addition, the novel σ1 agonist BD737 inhibited N‐methyl‐d‐aspartate‐stimulated release. Pentazocine inhibition was almost completely reversed by the σ antagonists NPC‐16377 and opipramol. A 1 µM concentration of the phencyclidine receptor‐selective ligand MK‐801 inhibited ∼65% of N‐methyl‐d‐aspartate‐stimulated release. These results suggest that σ receptors may play a role in modulating arachidonic acid release in cerebellar granule cells. Copyright © 1994, Wiley Blackwell. All rights reserve

Release of [\u3csup\u3e3\u3c/sup\u3eH]dopamine from guinea pig striatal slices is modulated by sigma1 receptor agonists

Sigma receptors are found in motor and limbic areas in the brains of humans, non-human primates, and rodents. The most extensive pharmacological studies of ligand binding to sigma receptors have utilized brain tissue from guinea pigs, where two subtypes of sigma receptor, designated sigma, and sigma2, have been identified. Few functional roles for sigma receptors have been described. Their location in guinea pig striatum, a terminal field of dopaminergic projections arising from the substantia nigra, suggested that this tissue would be a logical choice in which to examine physiological properties of sigma receptor activation. We found that sigma, receptor agonists inhibited N-methyl-D-aspartate-stimulated [3H]dopamine release from guinea pig striatal slices in a concentration-dependent manner. The inhibition by sigma, receptor agonists was reversed by a selective sigma, receptor antagonist, as well as by a non-subtype-selective sigma receptor antagonist. The ability of agonists working through sigma, receptors, but not through sigma2 receptors, to inhibit the stimulated release of catecholamines appears to be a unique characteristic of guinea pig striatum. We have previously reported that in rat striatum and hippocampus, as well as in guinea pig nucleus accumbens, prefrontal cortex, and hippocampus, activation of either sigma receptor subtype inhibits such release. Stimulated release of [3H]dopamine from guinea Dig striatum was also inhibited by the phencyclidine receptor agonist dizocilpine, but this inhibition was not reversed by the sigma receptor antagonists. Therefore, the inhibition produced by sigma receptor agonists was not mediated via the phencyclidine binding site within the N-methyl-D-aspartate-operated cation channel. Our findings support the hypothesis that sigma receptor activation provides a mechanism of modulating dopamine release from striatum, and that striatal tissue from guinea pigs appears to be an appropriate model for characterizing sigma, receptor-mediated effects

Steroids modulate N-methyl-D-aspartate-stimulated [\u3csup\u3e3\u3c/sup\u3eH]dopamine release from rat striatum via σ receptors

Steroids have been proposed as endogenous ligands at σ receptors. In the current study, we examined the ability of steroids to regulate N-methyl-D-aspartate (NMDA)-stimulated [3H]dopamine release from slices of rat striatal tissue. We found that both progesterone and pregnenolone inhibit [3H]dopamine release in a concentration-dependent manner similarly to prototypical agonists, such as (+)-pentazocine. The inhibition seen by both progesterone and pregnenolone exhibits IC50 values consistent with reported Ki values for these steroids obtained in binding studies, and was fully reversed by both the σ1 antagonist 1-(cyclopropylmethyl)-4-2′-4′′flurophenyl)-2′oxoethyl) piperidine HBr (DuP734) and the σ2 antagonist 1′-[4-[1-(4-fluorophenyl)-1-Hindol-3-yl]-1-butyl] spiro[iso-benzofuran-1(3H), 4′piperidine] (Lu28-179). Lastly, to determine whether a protein kinase C (PKC) signaling system might be involved in the inhibition of NMDA-stimulated [3H]dopamine release, we tested the PKCβ-selective inhibitor 5,21:12,17-dimetheno-18H-dibenzo[i,o]pyrrolo[3,4-1][1,8]diacyclohexadecine-18, 20(19H)-dione,8-[(dimethylamin-o)methyl]-6,7,8,9,10, 11-hexahydro-monomethanesulfonate (9Cl) (LY379196) against both progesterone and pregnenolone. We found that LY379196 at 30 nM reversed the inhibition of release by both progesterone and pregnenolone. These findings support steroids as candidates for endogenous ligands at σ receptors

Neuropeptide Y-mediated enhancement of NMDA-stimulated [\u3csup\u3e3\u3c/sup\u3eH]dopamine release from rat prefrontal cortex is reversed by σ1 receptor antagonists

Sigma (σ) receptors are located in limbic areas, including the prefrontal cortex, where decreased dopamine levels have been linked to negative symptoms. Although the endogenous ligands for σ receptors are unknown, neuropeptide Y (NPY) has been named as the potential endogenous agonist at these receptors. NPY enhanced NMDA-stimulated [3H]dopamine release in rat prefrontal cortex. This was in contrast to the inhibition produced by the σ agonists (+)pentazocine and BD737. However, four σ antagonists, including one which is σ1 selective, that reverse (+)pentazocine- or BD737-mediated inhibition all reversed the NPY-mediated enhancement. In addition, PYX-1, a Y receptor antagonist, reversed both the (+)pentazocine- and BD737-mediated inhibition and the NPY-mediated enhancement of release. Peptide YY (PYY). [Leu34,Pro34]Npy and NPY13-36, did not mimic the effect of NPY. Our findings are consistent with NPY acting as an endogenous ligand for a subtype of a receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-I. These findings suggest a role for NPY, via σ receptors, as a modulator of dopamine levels in the prefrontal cortex