Biomaterial Database

Inhibition of 5-HT3 receptor cation channels by ifenprodil in excised patches of N1E-115 cells. 1998

M Barann, and H Bönisch, and B W Urban, and M Göthert

Institut für Pharmakologie und Toxikologie, Universität Bonn, Germany.

The patch-clamp technique was applied in out-side-out patches of N1E-115 mouse neuroblastoma cells to investigate the effects of ifenprodil [(+/-) erythreo-ifenprodil tartratel, a drug with neuroprotective properties in cerebral ischemia, on the inward currents through 5-HT3 receptor channels. A high time resolution was achieved by using a rapid solution exchange system (exchange rate <1 ms). Ifenprodil inhibited the peak currents evoked by 30 microM 5-HT in a concentration-dependent but voltage-independent manner. The effect was most potent when ifenprodil was continuously applied to the patches 45 s before and during the 2-s administration of 5-HT (IC50=16 microM) and it was only slightly less potent when it was applied during the 45 s prior to 5-HT only (IC50=29 microM). When applied in this manner, ifenprodil also produced a concentration-dependent increase of the onset time constant (tauON) of the 5-HT (30 microM)-induced currents. When the drug was exclusively co-applied with 5-HT, ifenprodil was least potent in inhibiting the peak currents (IC50=98 microM), and it had no effect on the current onset kinetics. All protocols of ifenprodil application accelerated current inactivation as reflected by a decrease of the current inactivation time constant (tauOFF). All effects of ifenprodil were reversible after washout periods of 2-5 min. In conclusion, the potency of ifenprodil in inhibiting the inward current through 5-HT3 receptor channels is strongly dependent on the application protocol: presence of the drug before the agonist-induced activation of the 5-HT3 receptor channels is necessary for a relatively potent inhibition of the 5-HT-induced peak current and is a prerequisite for the prolongation of tauON; in addition, a weak but fast inhibitory effect on the current amplitude and decay constant of the 5-HT-induced current was revealed by the experiments in which ifenprodil was exclusively present during exposure to 5-HT. Three alternatives compatible with the components of the ifenprodil effect have been discussed: (1) different effects of the two enantiomers, (2) action via two different mechanisms, and (3) operation via a single mechanism only.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D010880	Piperidines	A family of hexahydropyridines.
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
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
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D000317	Adrenergic alpha-Antagonists	Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.	Adrenergic alpha-Receptor Blockaders,alpha-Adrenergic Blocking Agents,alpha-Adrenergic Receptor Blockaders,alpha-Blockers, Adrenergic,Adrenergic alpha-Blockers,alpha-Adrenergic Antagonists,alpha-Adrenergic Blockers,Adrenergic alpha Antagonists,Adrenergic alpha Blockers,Adrenergic alpha Receptor Blockaders,Agents, alpha-Adrenergic Blocking,Antagonists, alpha-Adrenergic,Blockaders, Adrenergic alpha-Receptor,Blockaders, alpha-Adrenergic Receptor,Blockers, alpha-Adrenergic,Blocking Agents, alpha-Adrenergic,Receptor Blockaders, alpha-Adrenergic,alpha Adrenergic Antagonists,alpha Adrenergic Blockers,alpha Adrenergic Blocking Agents,alpha Adrenergic Receptor Blockaders,alpha Blockers, Adrenergic,alpha-Antagonists, Adrenergic,alpha-Receptor Blockaders, Adrenergic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured