Biomaterial Database

Responses to 5-hydroxytryptamine evoked in the hemisected spinal cord of the neonate rat. 1988

L A Connell, and D I Wallis

Department of Physiology, University College, Cardiff.

1. Superfusion of isolated hemisected spinal cord from neonate rats with 5-hydroxytryptamine (5-HT) (10(-6) to 10(-3) M) evoked concentration-related depolarizations. The maximal depolarization elicited by a concentration of 10(-4) M was 1.0 +/- 0.1 mV (mean +/- s.e.mean, n = 30). Noradrenaline in a similar range of concentrations also elicited depolarizations. 2. The depolarizations probably originate in motoneurones as a result of direct interaction of the amines with these cells, since responses were unaltered by tetrodotoxin (10(-7) M) or Ca2+-free/Mg2+-rich medium. 3. 5-Carboxamidotryptamine (5-CT), S(+)-alpha-methyl-5-hydroxytryptamine (alpha-Me5-HT) and 5-methoxytryptamine (5-MeOT) evoked similar depolarizations to 5-HT. Tryptamine evoked depolarizations of smaller maximal amplitude. 5-Hydroxytryptophan, 2-methyl-5-hydroxytryptamine, 8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide (8-OH-DPAT) and 5-methoxy-3-[1,2,3,6-tetrahydro-4-pyridinyl]-1-H-indole succinate (RU 24969) had no depolarizing action. 4. Concentration-response (CR) curves were determined for 5-HT, 5-CT, alpha-Me5-HT, 5-MeOT and tryptamine. The ED50 value for 5-HT was 20.5 +/- 1.2 microM. The equipotent molar ratios (EPMRs) for 5-CT and alpha-Me5-HT were close to unity, while 5-MeOT was approximately 3 times and tryptamine 13 to 14 times less potent than 5-HT. 5. The relative agonist potency of 5-HT with respect to other tryptamine analogues capable of depolarizing motoneurones was increased when 5-HT uptake was blocked by citalopram (10(-7) M). In the presence of citalopram, 5-HT was 2.7 times more potent than alpha-Me5-HT and 16.9 times more potent than 5-CT. The apparent order of potency was 5-HT greater than alpha-Me5-HT greater than 5-CT (greater than 5-MeOT much greater than tryptamine). 6. The monoamine oxidase inhibitor, pargyline (5 x 10(-4) M), had no effect on depolarizations to 5-HT, 5-CT or alpha-Me5-HT. 7. Methiothepin, 1 alpha H, 3 alpha, 5H-tropan-3-yl-3,5-dichlorobenzoate methanesulphonate (MDL 72222) and [3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester hydrochloride (ICS 205-930) had no effect on 5-HT depolarizations elicited in motoneurones. Ketanserin (0.75 x 10(-7) M to 10(-6) M) showed modest antagonistic action and depressed maximal response amplitude; the pIC50 was 6.5. 8. Methysergide (10-8 to 10- 7M) was a potent antagonist of responses to 5-HT. CR curves were displaced to the right and flattened in the presence of the antagonist. The pIC5o assessed from the effect on depolarizations evoked by 5-HT 1O-4M was 7.5. 9. It is concluded that 5-HT acts directly to depolarize mammalian spinal motoneurones through receptors that are also activated by 5-CT, alpha-MeS-HT and 5-MeOT and are blocked by methysergide. The receptor profile, although not 5-HT3-like, does not clearly coincide with that for either 5-HT1-like or 5-HT2 receptors.

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
D008297	Male		Males
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
D009467	Neuromuscular Depolarizing Agents	Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation.	Depolarizing Muscle Relaxants,Muscle Relaxants, Depolarizing,Depolarizing Blockers,Agents, Neuromuscular Depolarizing,Blockers, Depolarizing,Depolarizing Agents, Neuromuscular,Relaxants, Depolarizing Muscle
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
D010293	Pargyline	A monoamine oxidase inhibitor with antihypertensive properties.	Pargyline Hydrochloride,Hydrochloride, Pargyline
D004566	Electrodes	Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.	Anode,Anode Materials,Cathode,Cathode Materials,Anode Material,Anodes,Cathode Material,Cathodes,Electrode,Material, Anode,Material, Cathode
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
D000831	Animals, Newborn	Refers to animals in the period of time just after birth.	Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
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