title: Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery.
abstract: OBJECTIVE
  The aim was to clarify the inhibitory effect of the selective kappa agonist, spiradoline, on coronary arterial smooth muscle in relation to the intracellular Ca2+ concentration.
  
  
  METHODS
  The inhibitory effect of spiradoline was investigated (1) on the contractile response of pig coronary artery to the readmission of Ca2+, following initial exposure to Ca2+ free medium and depolarisation with 40 mM K+; (2) on the intracellular Ca2+ concentration as assessed using the fluorescent calcium indicator fura-2. Relaxant responses to spiradoline in isolated porcine coronary artery strips contracted with K+ and prostaglandin F2 alpha were also examined.
  
  
  METHODS
  Coronary arteries isolated from pigs of both sexes were used. The right and left circumflex coronary arteries were cut into 3 mm wide strips which were used to measure the change in contractile force and the intracellular Ca2+ concentration.
  
  
  RESULTS
  Prior treatment with spiradoline at 2 x 10(-6) mol.litre-1 or more inhibited the contractile response to the readmission of Ca2+ in porcine coronary artery exposed to Ca2+ free medium in the presence of high K+. Naloxone at 3 x 10(-4) mol.litre-1 did not reverse the inhibitory action of 2 x 10(-5) M spiradoline. Ca2+ induced contraction was inhibited completely by 10(-4) M spiradoline. Moreover, spiradoline caused relaxation in arterial preparations that had been contracted with K+ (15 to 25 mmol.litre-1) or prostaglandin F2 alpha (10(-6) to 3 x 10(-6) mol litre-1), greater relaxation being seen in the K+ induced contraction. The intracellular Ca2+ concentration was significantly lowered by 2 x 10(-5) M spiradoline.
  
  
  CONCLUSIONS
  The relaxant response of coronary artery to spiradoline is, in part, attributable to interference with Ca2+ entry into the arterial smooth muscle.
authors.affiliation: Department of Pharmacology, Upjohn Pharmaceuticals Ltd, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harasawa
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017473:Receptors, Opioid, kappa; D013552:Swine
chemical_list: D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C051272:spiradoline; D002118:Calcium