R. Hester, N. Satake, S. Shibata
Feb 1, 1986
Citations
0
Influential Citations
6
Citations
Quality indicators
Journal
British Journal of Pharmacology
Abstract
1 In rabbit aorta, pretreatment with 2‐aminoisoquinoline, 1.3 (2H.4H)‐dione (AQ, 10−5 M and 10−4 M) shifted the concentration‐response relationship to noradrenaline (NA, 10−9 M to 10−4 M) in a parallel manner whereas the agent (10−4 M) failed to affect the response to potassium and only slightly depressed Ca2+‐induced contractions in a Ca2+‐free medium in the presence of K+ (40 mM). 2 Ca2+‐entry blockers such as nifedipine and diltiazem (10−6 M and 10−5 M) had very weak or no apparent effects on the response to NA but markedly attenuated or abolished the K+‐ and Ca2+‐induced contractions. 3 Following incubation of tissues for 15 min in a Ca2+‐free medium with low EGTA (0.01 mM) and methoxyverapamil (D600, 10−5 M), NA (3 × 10−7 M) caused a phasic (transient) contraction and the subsequent application of Ca2+ (2mM) resulted in a tonic contraction. This NA‐induced, Ca2+‐dependent, D600‐insensitive contraction was inhibited by AQ (10−5 M and 10−4 M) in a concentration‐dependent manner. This suggests that the inhibitory action of AQ may be related to Ca2+ entry through specific receptor activated pathways. 4 Following incubation of tissues for 30 min in a Ca2+‐free medium with high EGTA (2.0 mM), NA (10−5 M) caused a contraction of rabbit aorta which is dependent upon release of intracellular Ca2+, but the response was 50% to 60% less than that in a normal medium. This contraction was inhibited by AQ (10−5 M and 10−4 M) and nitroglycerin (10−5 M) but not by nifedipine or diltiazem. The inhibitory action of combined treatment with AQ and nitroglycerin (10−5 M) on the response to NA was not different from that of either agent alone. 5 These results suggest that AQ may have inhibitory actions on the release of intracellular Ca2+ and also on Ca2+‐entry through D600‐insensitive, receptor‐activated Ca2+ pathways in rabbit aorta.