title: Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle.
abstract: OBJECTIVE
  The effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent-kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated.
  
  
  METHODS
  Tracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution.
  
  
  RESULTS
  TCCA reduced the contractions induced by electrical field stimulation, relaxed K(+)-induced contractions, and inhibited both phasic and tonic components of the K(+)- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K(+) in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca(2+)-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) and receptor-operated Ca(2+) channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca(2+)-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 µm) induced contraction, but with slight potency.
  
  
  CONCLUSIONS
  TCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP(3)-induced Ca(2+) release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca(2+).
authors: Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, Brazil.
authors: Liza Araújo
authors: LA
authors: Aguiar
authors: Romulo Sousa
authors: RS
authors: Porto
authors: Saad
authors: S
authors: Lahlou
authors: Vânia Marilande
authors: VM
authors: Ceccatto
authors: Roseli
authors: R
authors: Barbosa
authors: Telma Leda Gomes
authors: TL
authors: Lemos
authors: Hélcio Silva
authors: HS
authors: dos Santos
authors: Andrelina Noronha
authors: AN
authors: Coelho-de-Souza
authors: Pedro Jorge Caldas
authors: PJ
authors: Magalhães
authors: Walter Araújo
authors: WA
authors: Zin
authors: José Henrique
authors: JH
authors: Leal-Cardoso
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D029802:Croton / Q000737:chemistry*; D045786:Diterpenes, Kaurane / Q000302:isolation & purification / Q000494:pharmacology*; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: C576351:7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid; D015220:Calcium Channels; D002273:Carcinogens; D045786:Diterpenes, Kaurane; D007295:Inositol Phosphates; D010276:Parasympatholytics; D010936:Plant Extracts; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D004837:Epinephrine