title: Gut modulatory effects of Daphne oleoides are mediated through cholinergic and Ca++ antagonist mechanisms.
abstract: BACKGROUND
  The present study describes the spasmogenic and spasmolytic activities of Daphne oleoides Schreb. (Thymelaeaceae), exploring the possible underlying pharmacological mechanisms.
  
  
  OBJECTIVE
  Pharmacological investigation of Daphne oleoides to provide evidence for its therapeutic application in gastrointestinal motility disorders.
  
  
  METHODS
  Methanol crude extract of Daphne oleoides (Do.Cr) was studied in gastrointestinal isolated tissues.
  
  
  RESULTS
  In spontaneously contracting rabbit jejunum preparations, Do.Cr at 0.3-3.0 mg/mL caused moderate stimulation, followed by relaxant effect at the next higher concentrations (5.0-10 mg/mL). In presence of atropine, spasmogenic effect was blocked and the relaxation was emerged, suggesting that the spasmogenic effect of Daphne oleoides is mediated through activation of muscarinic receptors. When tested against the high K+ (80 mM)-induced contractions, Do.Cr (0.3-5.0 mg/mL), like verapamil, inhibited the induced contractions, suggesting Ca++ channel blockade (CCB) effect. The CCB effect was further confirmed when pre-treatment of the tissue with Do.Cr shifted the Ca++ concentration-response curves to the right, similar to that caused by verapamil.
  
  
  CONCLUSIONS
  These results indicate that Daphne oleoides exhibits gut excitatory and inhibitory effects, occurred via cholinergic and Ca++ antagonistic pathways, respectively.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi, Pakistan.
authors.forename: Arif-ullah
authors.initials: AU
authors.lastname: Khan
authors.forename: Farman
authors.initials: F
authors.lastname: Ali
authors.forename: Dilfaraz
authors.initials: D
authors.lastname: Khan
authors.forename: Anwarul-Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D018678:Cholinergic Agents / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D032364:Daphne; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000188:drug therapy; D005769:Gastrointestinal Motility / Q000187:drug effects; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D010944:Plants; D011817:Rabbits
chemical_list: D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D010276:Parasympatholytics; D010936:Plant Extracts