Different effects of R 56865 and calcium entry blockers on K+- and noradrenaline-induced contractions and 45Ca uptake in rat aorta.
The effects of R 56865, nifedipine, verapamil, diltiazem and flunarizine on K+- and NA-induced contractions and K+-induced 45Ca uptake were compared in the isolated rat aorta. The calcium entry blockers concentration dependently inhibited the K+-induced contraction and 45Ca uptake over the same dose-range. R 56865 inhibited the K+-induced 45Ca uptake, but only partly inhibited the K+-induced contraction. The calcium entry blockers caused a slight rightward shift and a depression of the maximum of the concentration-response curve for the NA-induced contraction. In contrast, R 56865 caused a strong, dose-dependent rightward shift and a depression of the maximum, 10(-6) and 10(-5) M being equieffective. The effects of R 56865 and nifedipine were independent of each other. Nevertheless, the NA-induced increase in 45 Ca uptake, a putative model for Ca influx, was attenuated by R 56865. In conclusion, R 56865 is a weak inhibitor of the K+-induced Ca influx but is without effect on the NA-induced Ca influx. The discrepancy between its effects on K+-induced contractions and 45Ca uptake may be explained by an inhibition of the uptake of 45Ca from the cytosol into the 45Ca pool. The interaction between R 56865 and the alpha 1-adrenoceptor-mediated contractions may be explained by an action at a site that is distinct from the NA-binding-site on the alpha 1-adrenoceptor.
Koch
P
P
Janssen Research Foundation, Neuss, F.R.G.
Wilhelm
D
D
Wermelskirchen
D
D
Nebel
U
U
Wilffert
B
B
Peters
T
T
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D010880:Piperidines; D013844:Thiazoles; C054551:R 56865; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine