Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery.
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.
Harasawa
Y
Y
Department of Pharmacology, Upjohn Pharmaceuticals Ltd, Ibaraki, Japan.
Kimura
M
M
Hayashi
S
S
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
D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C051272:spiradoline; D002118:Calcium