Alpha 1A-adrenoceptor subtype effectively increases Ca(2+)-sensitivity for contraction in rabbit thoracic aorta.
1. Norepinephrine and phenylephrine increase cytosolic Ca2+ concentration ([Ca2+]i) and muscle tension, which shows positive correlation between [Ca2+]i and tension development. 2. The slopes of regression lines between [Ca2+]i and tension development for norepinephrine and phenylephrine in tissues treated with an irreversible alpha 1B-adrenoceptor selective blocking agent, 10(-4) M chloroethylclonidine, were significantly steeper than those with untreated tissues. 3. Myosin light chain kinase inhibitors, KT5926 (3 x 10(-6) M) and K252a (10(-6) M) more selectively reduced the contraction produced by norepinephrine (3 x 10(-7) M) than that produced by clonidine (3 x 10(-6) M). 4. In the chloroethylclonidine-treated tissues, KT5926 and K252a did not tend to affect the contraction induced by norepinephrine and clonidine. 5. These results suggest that the contractile response through the alpha 1A-adrenoceptor subtype causes a greater muscle tension than that through the alpha 1B-subtype at the same level of [Ca2+]i, and that the alpha 1A-adrenoceptor subtype mainly activates myosin light chain kinase independent pathways of contractile mechanisms in vascular smooth muscle of rabbit.
Satoh
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kokubu
N
N
Matsuo
K
K
Takayanagi
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012680:Sensitivity and Specificity
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; D018340:Receptors, Adrenergic, alpha-1; C063769:KT 5926; D010656:Phenylephrine; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine