title: Acute, chronic and differential effects of several anesthetic barbiturates on glutamate receptor activation in neuronal culture.
abstract: The acute and chronic effects of several anesthetic barbiturates, in therapeutic concentrations, on the excitatory amino acid (EAA)-induced elevation of intracellular calcium levels ([Ca2+]i) were examined in neuronal tissue culture. The ultrashort-acting barbiturate, thiamylal, was effective in blocking elevations of [Ca2+]i induced by kainate, N-methyl-D-aspartate (NMDA), and quisqualate or by membrane depolarization with 40 mM KCl. The structurally similar barbiturate, secobarbital which differs from thiamylal only by having an oxygen in place of a sulfur, was able to block elevations induced by the above EAAs but was less effective than thiamylal and did not significantly reduce [Ca2+]i that resulted from membrane depolarization with KCl. Pentobarbital, while differing from secobarbital by only a methyl group, was without effect on either the NMDA- or 40 mM KCl-induced elevations of [Ca2+]i. By contrast, cyproheptadine, a compound that has been shown to block Ca2+ channels, has a different profile from the above barbiturates in that cyproheptadine is more effective in blocking elevation of [Ca2+]i induced by membrane depolarization with KCl while the barbiturates are more effective in reducing [Ca2+]i induced by EAAs. An anticonvulsant barbiturate, phenobarbital, did not reduced elevations of [Ca2+]i induced by any EAA tested or by membrane depolarization with KCl. When cells were treated chronically with thiamylal for 4 days, 2-6 h after the abrupt drug withdrawal there was a hyperresponsiveness to the elevations of [Ca2+]i induced by both kainate and NMDA but not by quisqualate. A similar hyperresponsiveness was not seen after the chronic treatment with phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.forename: P P
authors.initials: PP
authors.lastname: McCaslin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D003533:Cyproheptadine / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D012631:Secobarbital / Q000494:pharmacology*; D013840:Thiamylal / Q000494:pharmacology*
chemical_list: D005971:Glutamates; D017470:Receptors, Glutamate; D013840:Thiamylal; D012631:Secobarbital; D003533:Cyproheptadine; D016202:N-Methylaspartate; D011189:Potassium Chloride; D016318:Quisqualic Acid; D010424:Pentobarbital; D007608:Kainic Acid; D002118:Calcium