Alpha 1-adrenergic partial agonists utilize cytosolic Ca2+ more effectively for contraction in aortic smooth muscle.
Fura 2 loaded thoracic aorta strips from rabbits were used. Norepinephrine, phenylephrine, clonidine, and tizanidine induced an increase in cytosolic Ca2+ concentration [( Ca2+]i) and muscle tension in a concentration-dependent manner. A positive correlation between [Ca2+]i and tension development owing to the agonists was noted. The slope of regression lines between [Ca2+]i and tension development for clonidine and tizanidine, alpha 1-adrenergic partial agonists, were significantly steeper than those for norepinephrine and phenylphrine, alpha 1-adrenergic full agonists. The intrinsic activities of the partial agonists obtained from tension development were greater than those from changes in [Ca2+]i. These results suggest that the partial agonists cause a greater muscle tension than the full agonists at the same level of [Ca2+]i.
Takayanagi
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I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Onozuka
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S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D010643:Phenoxybenzamine; D010656:Phenylephrine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine