Ca-entry blockers, verapamil and diltiazem, on alpha 1-adrenoceptors in thoracic aorta, renal artery and portal vein from rabbit.
1. Verapamil caused a parallel shift of the concentration-response curve for norepinephrine in rabbit thoracic aorta and the reduction in norepinephrine-induced maximum response with shifts of the concentration-response curve for norepinephrine in renal artery and portal vein. 2. Diltiazem was without any effects on the response of thoracic aorta to norepinephrine, while the responses of renal artery and portal vein to norepinephrine were inhibited noncompetitively by diltiazem. 3. Verapamil but not diltiazem diminished markedly dibenamine-induced inhibition of maximum response to norepinephrine in all the preparations used. 4. Specific bindings of [3H]prazosin to both the membrane fractions derived from thoracic aorta and renal artery were displaced concentration-dependently by verapamil and diltiazem, but the effective concentrations of diltiazem were more than those for Ca-entry blocking activity. 5. These results suggest that verapamil might antagonize norepinephrine at alpha 1-adrenoceptors and the effective concentration for Ca-entry blocking activity of diltiazem were less than those for the interaction of diltiazem with alpha 1-adrenoceptors.
Koike
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
Ohashi
M
M
Nakazawa
T
T
Kumagai
N
N
Kishii
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D014700:Verapamil; D004110:Diltiazem; D009638:Norepinephrine