Inhibition by phencyclidine of excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens

The effects of phencyclidine (PCP) on the release of acetylcholine and dopamine, stimulated by excitatory amino acid agonists was examined in slices of nucleus accumbens of the rat. In slices incubated in [3H]choline or [3H]dopamine, the amount of tritium efflux produced by 1 mM N-methyl-D-aspartate (NMDA), kainic acid (KA) or quisqualic acid (QA) was compared with that produced in the presence of varying concentrations of phencyclidine. N-Methyl-D-aspartate stimulated the calcium-dependent release of both ACh and DA, which was completely inhibited by physiological concentrations of magnesium and inhibited by 2-aminophosphonovalerate (2-APV). Kainic acid- and quisqualic acid-stimulated release of ACh and DA was partially inhibited by magnesium or by 2-APV. Phencyclidine inhibited NMDA-stimulated release of ACh and DA with IC50's around 100 nM. Phencyclidine (0.1 microM) also significantly inhibited kainic acid and quisqualic acid-induced release of ACh in magnesium-free but not magnesium-containing buffer, suggesting that the effect of PCP on kainic acid- and possibly quisqualic acid-stimulated release of ACh is on that part of the response which is mediated by NMDA receptors. The results suggest that the inhibition by PCP of the release of ACh and DA in the nucleus accumbens is selective for NMDA-type receptors.     

The impact of intra-operative transoesophageal echocardiography on cardiac surgical practice

The use of transoesophageal echocardiography during cardiac surgery has increased dramatically and it is now widely accepted as a routine monitoring and diagnostic tool. A prospective study was carried out between September 2004 and September 2007, and included all patients in whom intra-operative echocardiography was performed, 2 473 (44%) out of a total of 5 591 cases. Changes to surgery were subdivided into predictable (where echocardiographic examination was planned specifically to guide surgery) and unpredictable (new pathology not diagnosed pre-operatively). A change in the planned surgical procedure was documented in 312 (15%) cases. In 216 (69%) patients the changes were predictable and in 96 (31%) they were unpredictable. The number of predictable changes increased between 2004–5 and 2006–7 (8% vs 13%, p = 0.025). In these cases, intra-operative echocardiography was specifically requested by the surgeon to help determine the operative intervention. This has implications for consent and operative risk, which have yet to be fully determined.     

Effect of epinephrine on intrathecal fentanyl analgesia in patients undergoing postpartum tubal ligation

Eighty women receiving spinal anesthesia for postpartum tubal ligation were entered into a double-blind, randomized protocol studying the effects of epinephrine on intrathecal fentanyl-induced postoperative analgesia. All patients received 70 mg hyperbaric lidocaine with either 0.2 mg epinephrine (LE), 10 micrograms fentanyl (LF), epinephrine and fentanyl (LFE), or 0.4 ml saline (L). Onset and regression of anesthesia, degree of intraoperative comfort, incidence of pruritus, and extent of postoperative analgesia were evaluated. The simultaneous administration of epinephrine and fentanyl prolonged the duration of complete analgesia (137 +/- 47 min (LFE); 76 +/- 32 min (LE); 85 +/- 44 min (LF); 65 +/- 36 min (L)) and the duration of effective analgesia (562 +/- 504 min (LFE); 227 +/- 201 min (LE); 203 +/- 178 min (LF); 198 +/- 342 min (L)). Administration of epinephrine decreased the incidence of pruritus associated with intrathecal fentanyl (1/18 (LFE); 1/21 (LE); 8/19 (LF); 2/19 (L)).     

Phencyclidine selectively inhibits N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release

We have reported previously that phencyclidine (PCP) antagonizes N-methyl-D-aspartate (NMDA)-induced release of dopamine and acetylcholine from slices of rat striatum and nucleus accumbens. In the present experiments, we examined the effect of PCP on NMDA and kainic acid (KA)-induced release of [3H]norepinephrine (NE) from superfused rat hippocampal slices. NMDA and KA stimulated the efflux of NE with EC50 values of 192 and 245 microM, respectively. The presence of 1.2 mM MgCl2 in the buffer abolished NMDA-induced release but had little effect on KA-induced release. PCP inhibited the release of [3H]NE induced by 100 microM NMDA with an IC50 of 46 nM, but had no effect on the release of NE stimulated by 300 microM KA. 2-Aminophosphonovalerate antagonized NMDA-induced release, producing a parallel shift to the right in the concentration-response curve. However, PCP shifted the concentration-response curve to the right in a nonparallel fashion. Drugs with PCP-like properties, such as dexoxadrol and cyclazocine, inhibited NMDA-induced release, whereas related drugs such as levoxadrol, ethylketocyclazocine and morphine, which are not PCP-like, had no effect. These data suggest that PCP is a potent, selective, noncompetitive inhibitor of amino acid-induced [3H]NE release and that this action of PCP is mediated through the PCP/sigma receptor.     

Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs

In the present study, the authors found that, in Mg++-free buffer, N-methyl-D-aspartate (NMDA) was able to evoke the Ca++-dependent and tetrodotoxin-sensitive release of striatal acetylcholine (ACh), presumably via interaction with receptors on cholinergic interneurons. In Mg++-free buffer containing pargyline, NMDA also evoked a Ca++-dependent and tetrodotoxin-sensitive release of striatal [3H]dopamine (DA). Phencyclidine (PCP) and physiological concentrations of Mg++ (1.2 mM) also inhibited ACh release evoked by L-glutamate, L-aspartate and DL-homocysteate, but not ACh release evoked by the glutamate analogs quisqualate and kainate, suggesting that PCP is selective for the magnesium-sensitive, NMDA-preferring glutamate-aspartate receptor subtype. Comparison of PCP inhibition of NMDA-stimulated ACh and DA release with that produced by the competitive NMDA antagonist 2-amino-5-phosphonovalerate indicates that PCP is probably not altering release by a direct action on the NMDA recognition site. The ability of 2-amino-5-phosphonovalerate, but not PCP, to prevent desensitization of NMDA-induced ACh release is consistent with this interpretation. Binding studies did, however, reveal a reduction in the apparent affinity of the PCP binding site by high concentrations of NMDA. This may suggest an allosteric link between the PCP-sigma receptor and the NMDA-type glutamate-aspartate receptor. The receptors mediating excitatory amino acid-induced DA release were somewhat less selective than those on cholinergic neurons in their sensitivity to both Mg++ and PCP. Structure-activity-relationship studies suggested that the inhibition off ACh and DA release evoked by NMDA involves biding to the PCP-sigma receptor.(ABSTRACT TRUNCATED AT 250 WORDS)