Biomaterial Database

Effects of serotonergic agents on neuronal nicotinic acetylcholine receptors. 1995

J García-Colunga, and R Miledi

Department of Psychobiology, University of California, Irvine 92717-4550, USA.

In Xenopus oocytes expressing neuronal nicotinic acetylcholine receptors (nAcChoRs), made up of alpha 2 and beta 4 subunits, acetylcholine (AcCho) elicited ionic membrane currents (AcCho currents) that were modulated by serotonergic agents. Both agonists and antagonists specific for various serotonin (5-hydroxytryptamine, 5HT) receptor subtypes interacted directly with alpha 2 beta 4 nAcChoRs: 5HT, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, methysergide, spiperone, and ketanserin reversibly reduced the amplitude of AcCho currents and accelerated their decay. The AcCho-current time course decayed with two exponential functions. In the presence of 5HT, the fast time constant of current decay (tau f) was not greatly modified, but the slow time constant (tau s) was reduced. With AcCho and 5HT both at 100 microM, tau s was reduced from 140 s to 85 s. The order of potency for inhibition of AcCho current amplitudes was (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin > methysergide > spiperone > ketanserin > 5HT. The inhibition was voltage-dependent but the magnitude of the voltage dependence for the different blockers did not correspond to their blocking potency: e.g., the block with spiperone was stronger than with 5HT, but it was less voltage-dependent. Our results suggest that serotonergic agents block neuronal nAcChoRs in a noncompetitive manner, similar to the block of muscle nAcChoR by curare and other substances. These results show that neuronal nAcChoR channels that have been activated by their specific neurotransmitter may be modulated by nonspecific neurotransmitters and their antagonists. These effects may help to better understand brain functions as well as the mode of action of the many serotonergic agents that are used in medical practice.

UI	MeSH Term	Description	Entries
D007650	Ketanserin	A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.	3-(2-(4-(4-Fluorobenzoyl)piperidinol)ethyl)-2,4(1H,3H)-quinazolinedione,R-41,468,R-41468,R 41,468,R 41468,R41,468,R41468
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
D008784	Methysergide	An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.	Dimethylergometrin,Methylmethylergonovine,Deseril,Desril,Désernil-Sandoz,Methysergide Dimaleate,Methysergide Maleate,Sansert,UML-491,Dimaleate, Methysergide,Désernil Sandoz,Maleate, Methysergide,UML 491,UML491
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009865	Oocytes	Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).	Ovocytes,Oocyte,Ovocyte
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
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
D004553	Electric Conductivity	The ability of a substrate to allow the passage of ELECTRONS.	Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D005260	Female		Females
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