Effects of ethanol on tryptophan hydroxylase activity from striate synaptosomes.
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Alcohols↗
Biomedical subjects
M A Rogawski
Publications and source records attributed to M A Rogawski.
Cholecystokinin octapeptide: effects on the excitability of cultured spinal neurons.
The actions of cholecystokinin octapeptide (CCK) on the membrane properties of mouse spinal neurons grown in monolayer culture were examined using intracellular recording techniques. In a subpopulation of cells, application of CCK (0.2-100 micron) by pressure ejection from micropipettes produced a small (approximately 2 mV) membrane depolarization that was accompanied by a decrease in membrane conductance (approximately 11 percent). These effects were associated with an enhanced tendency of the cells to generate action potentials when stimulated with intracellular depolarizing current. The unsulfated analog of CCK, which possesses weak biological activity in the gut, had little or no effect on cultured spinal neurons. A number of differences were noted between the responses to CCK and the excitatory amino acid glutamate. First, the effects of CCK were more delayed in onset (approximately 17 sec) and prolonged in duration (approximately 124 sec). Second, the depolarizations produced by glutamate were of larger magnitude and associated with variable effects on membrane conductance. Third, the response to CCK showed tachyphylaxis with repeated applications whereas glutamate remained effective as often as it was applied. It is concluded that CCK facilitates the excitability of spinal neurons in a manner distinct from that of the conventional excitant glutamate.
Animals↗
GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro.
A non-NMDA and non-AMPA receptor mediated excitatory synaptic response was identified in intracellularly recorded basolateral amygdala (BLA) neurons in an in vitro slice preparation. Synaptic potentials were evoked by stimulation of either the external capsule (EC) or basal amygdala (BA). NMDA and GABA(A) receptors were blocked by inclusion of 100 microM (+/-)-2-amino-5-phosphonopentanoic acid and 10 microM bicuculline in the perfusion solution. The AMPA receptor-selective allosteric antagonists GYKI 52466 (50 microM) and GYKI 53655 (50 microM) partially suppressed depolarizing synaptic responses evoked by single shock EC stimulation, but fully blocked synaptic responses evoked by BA stimulation. In recordings carried out in the presence of the AMPA receptor antagonists, EC stimulation with pulse trains (5-8 pulses at 50-100 Hz) evoked a large increase in the amplitude of synaptic responses. The AMPA receptor-independent component of the train-induced synaptic response had a null potential near 0 mV. Such AMPA receptor-independent, train-evoked synaptic responses were largely blocked by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM; 85 +/- 4%). In addition, the responses were blocked by the GluR5-selective kainate receptor antagonist LY293558 (10 microM; 95 +/- 2%). These results indicate that a component of the EC (but not the BA) synaptic response is mediated by kainate receptors containing the GluR5 subunit.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Anticonvulsant 1-phenylcycloalkylamines: two analogues with low motor toxicity when orally administered.
1-Phenylcyclohexylamine (PCA) and its analogues 1-phenylcyclopentylamine (PPA) and 1-(3-fluorophenyl)cyclohexylamine (3-F-PCA) are potent anticonvulsants in the mouse maximal electroshock (MES) seizure test. Unlike the structurally related dissociative anesthetic phencyclidine (PCP), however, which produces motor toxicity at anticonvulsant doses, PCA, PPA, and 3-F-PCA protect against MES seizures at 2.2- to 3.5-fold lower doses than those that cause motor toxicity when administered intraperitoneally (i.p.). In the present study, we evaluated the oral anticonvulsant activity of PCA, PPA, and 3-F-PCA in mice; we also examined 3-F-PCA in rats. All the compounds were orally active in the mouse MES seizure test (ED50 values 14.5, 53.4, and 26.7 mg/kg, respectively). Moreover, 3-F-PCA was especially potent in rats, either when administered i.p. (ED50 0.4 mg/kg vs. 9.4 mg/kg in mice) or orally (ED50 0.8 mg/kg). Surprisingly, however, oral PPA failed to cause motor toxicity in mice even at doses that were many times higher than those that were protective in the MES test (TD50 greater than 300 mg/kg). In rats, 3-F-PCA also showed a strikingly low oral toxicity (TD50 greater than 50 mg/kg) in relation to its potency as an anticonvulsant. Like PCP, PCA analogues block N-methyl-D-aspartate (NMDA)-induced behavioral effects and lethality in mice. Moreover, in vitro studies indicate that the compounds act as uncompetitive antagonists of the NMDA receptor-channel complex. Therefore, their anticonvulsant activity may, at least in part, relate to an interaction with NMDA receptors.
Administration, Oral↗