Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery
التفاصيل البيبلوغرافية
العنوان:
Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery
Study objective — The aim was to clarify the inhibitory effect of the selective κ agonist, spiradoline, on coronary arterial smooth muscle in relation to the intracellular Ca2+ concentration. Design — 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 F2α were also examined. Experimental material — 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. Measurements and main results — Prior treatment with spiradoline at 2 × 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 × 10−4 mo·litre−1 did not reverse the inhibitory action of 2 × 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 F2α (10−6 to 3 × 10−6 mol litre−1), greater relaxation being seen in the K+ induced contraction. The intracellular Ca2+ concentration was significantly lowered by 2 × 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.