Effects of propofol and thiopentone on potassium- and carbachol-evoked [3H]noradrenaline release and increased [Ca2+]i from SH-SY5Y human neuroblastoma cells. 1996

D G Lambert, and J M Willets, and R Atcheson, and C Frost, and D Smart, and D J Rowbotham, and G Smith
University Department of Anaesthesia, Leicester Royal Infirmary, UK.

We have examined the effects of two intravenous anaesthetic induction agents, propofol and thiopentone, on K+ and carbachol evoked [3H]noradrenaline release from a human neuroblastoma cell line, SH-SY5Y. In this model, we have previously demonstrated that K+ evoked [3H]noradrenaline release was dependent on Ca2+ entry and carbachol evoked release was extracellular Ca(2+)- independent. Propofol inhibited K+ (100 mM)-evoked (IC50 of 42 +/- 11 microM), but not carbachol (1 mM)-evoked, [3H]noradrenaline release. Thiopentone inhibited both K+- and carbachol-evoked release with IC50 values of 116 +/- 15 microM and 169 +/- 39 microM, respectively. These inhibitory effects were not due to changes in the release dynamics, as assessed using perfused cells. Furthermore, thiopentone inhibition of carbachol-evoked release was not due to muscarinic receptor antagonism. Both propofol and thiopentone caused noncompetitive inhibition of K+-stimulated Ca2+ influx, with IC50 values of 127 +/- 7 microM and 121 +/- 10 microM, respectively. These effects were not due to interaction with GABAA receptors, but suggest that both compounds block voltage-sensitive Ca2+ channels. Thiopentone, but not propofol, inhibited carbachol-stimulated increased intracellular Ca2+ concentrations in the presence and absence of extracellular Ca2+. However, thiopentone had no effect on carbachol-stimulated inositol (1,4,5)-triphosphate formation, suggesting that thiopentone may directly inhibit Ca2+ release from intracellular stores.

UI MeSH Term Description Entries
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013874 Thiopental A barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration. Penthiobarbital,Thiomebumal,Thiopentobarbital,Bomathal,Nesdonal,Pentothal,Pentothal Sodico,Sodipental,Thionembutal,Thiopental Nycomed,Thiopental Sodium,Thiopentone,Tiobarbital Braun,Trapanal
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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