Biomaterial Database

Nondepolarizing neuromuscular blockers inhibit the serotonin-type 3A receptor expressed in Xenopus oocytes. 2000

K T Min, and C L Wu, and J Yang

Departments of Anesthesiology and Pharmacology/Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.

Molecular cloning and sequence comparison indicates a high degree of structural homology between muscle nicotinic acetylcholine (nACh) and serotonin-type 3 (5-HT(3A)) receptors, both members of the direct ligand-gated family of ion channels. Because of the structural similarities and common evolutionary origin of these receptors, neuromuscular blockers (competitive nACh antagonists) may demonstrate pharmacologic cross talk and exhibit attributes of 5-HT(3A) receptor antagonists. We examined six clinically-used neuromuscular blockers for their ability to antagonize currents flowing through the 5-HT(3A) receptors in voltage clamped Xenopus oocytes. The neuromuscular blockers reversibly inhibited the 5-HT(3A) receptor-gated current in the rank order potency of (IC50 mean +/- SEM): d-tubocurarine (0.046 +/- 0.003 microM), atracurium (0.40 +/- 0.03 microM), mivacurium (15.1 +/- 2.93 microM), vecuronium (16.3 +/- 2.24 microM), and rocuronium (19.5 +/- 2.31 microM). Gallamine was essentially inactive as a 5-HT(3A) receptor antagonist with an extrapolated IC50 of 1170 microM. We demonstrate that drugs classically known as competitive nACh receptor antagonists also block 5-HT(3A) receptors. It is likely that certain neuromuscular blockers share pharmacological properties with 5-HT(3A) receptor antagonists, such as a reduction in postoperative nausea and vomiting. With careful drug selection, pharmacological cross talk could potentially be used to minimize polypharmacy and optimize patient management. CONCLUSIONS Muscle nicotinic acetylcholine and serotonin-type 3A (5-HT(3A)) receptors are similar. Therefore neuromuscular relaxants may block 5-HT(3A) receptors. Our pharmacological study demonstrates that neuromuscular relaxants, as with ondansetron, are 5-HT(3A) receptor antagonists. It is likely that certain neuromuscular relaxants exhibit ondansetron-like clinical properties, such as reduction in postoperative nausea and vomiting.

UI	MeSH Term	Description	Entries
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
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
D003473	Neuromuscular Nondepolarizing Agents	Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants.	Curare-Like Agents,Curariform Drugs,Muscle Relaxants, Non-Depolarizing,Neuromuscular Blocking Agents, Competitive,Nondepolarizing Blockers,Agents, Curare-Like,Agents, Neuromuscular Nondepolarizing,Blockers, Nondepolarizing,Curare Like Agents,Drugs, Curariform,Muscle Relaxants, Non Depolarizing,Non-Depolarizing Muscle Relaxants,Nondepolarizing Agents, Neuromuscular
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
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
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
D012702	Serotonin Antagonists	Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.	5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin
D014981	Xenopus	An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
D015640	Ion Channel Gating	The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.	Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings
D044406	Receptors, Serotonin, 5-HT3	A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.	Serotonin 3 Receptor,5-HT3 Receptor,5-Hydroxytryptamine-3 Receptor,Receptor, Serotonin 3,Receptor, Serotonin, 5-HT3 Subunit A,Receptor, Serotonin, 5-HT3 Subunit B,Receptor, Serotonin, 5-HT3 Subunit C,Receptor, Serotonin, 5-HT3 Subunit D,Receptor, Serotonin, 5-HT3 Subunit E,Receptor, Serotonin, 5-HT3A,Receptor, Serotonin, 5-HT3B,Receptor, Serotonin, 5-HT3C,Receptor, Serotonin, 5-HT3D,Receptor, Serotonin, 5-HT3E,Serotonin 3 Receptors,5 HT3 Receptor,5 Hydroxytryptamine 3 Receptor,Receptor, 5-Hydroxytryptamine-3,Receptors, Serotonin 3