title: Characterization of a new muscarinic toxin from the venom of the Brazilian coral snake Micrurus lemniscatus in rat hippocampus.
abstract: OBJECTIVE
  We have isolated a new muscarinic protein (MT-Mlα) from the venom of the Brazilian coral snake Micrurus lemniscatus.
  
  
  METHODS
  This small protein, which had a molecular mass of 7,048Da, shared high sequence homology with three-finger proteins that act on cholinergic receptors. The first 12 amino acid residues of the N-terminal sequence were determined to be: Leu-Ile-Cys-Phe-Ile-Cys-Phe-Ser-Pro-Thr-Ala-His.
  
  
  RESULTS
  The MT-Mlα was able to displace the [(3)H]QNB binding in the hippocampus of rats. The binding curve in competition experiments with MT-Mlα was indicative of two types of [(3)H]QNB-binding site with pK(i) values of 9.08±0.67 and 6.17±0.19, n=4, suggesting that various muscarinic acetylcholine receptor (mAChR) subtypes may be the target proteins of MT-Mlα. The MT-Mlα and the M(1) antagonist pirenzepine caused a dose-dependent block on total [(3)H]inositol phosphate accumulation induced by carbachol. The IC(50) values for MT-Mlα and pirenzepine were, respectively, 33.1 and 2.26 nM. Taken together, these studies indicate that the MT-Mlα has antagonist effect on mAChRs in rat hippocampus.
  
  
  CONCLUSIONS
  The results of the present study show, for the first time, that mAChRs function is drastically affected by MT-Mlα since it not only has affinity for mAChRs but also has the ability to inhibit mAChRs.
authors: Laboratory of Pharmacology, Instituto Butantan, São Paulo, Brazil.
authors: Daniel Coelho
authors: DC
authors: da Silva
authors: Wyara Aparecida Araújo
authors: WA
authors: de Medeiros
authors: Isabel de Fátima Correia
authors: Ide F
authors: Batista
authors: Daniel Carvalho
authors: DC
authors: Pimenta
authors: Ivo
authors: I
authors: Lebrun
authors: Fernando Maurício Francis
authors: FM
authors: Abdalla
authors: Maria Regina Lopes
authors: MR
authors: Sandoval
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001938:Brazil; D004546:Elapid Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D017815:Elapidae; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010890:Pirenzepine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004546:Elapid Venoms; D007295:Inositol Phosphates; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; C053972:micrurus venom; D010890:Pirenzepine