Histamine concentration and Ca2+ mobilization in arterial smooth muscle.
Smooth muscle contraction is dependent on Ca2+ entry from the extracellular space or release from intracellular stores. The sensitivity of these Ca2+ sources to agonist concentration was evaluated by measuring myoplasmic [Ca2+] (as estimated by aequorin), myosin phosphorylation, and isometric stress in the swine carotid media. High histamine concentrations produced transient elevations in [Ca2+] and phosphorylation with rapid generation of near maximal stress. Lower histamine concentrations produced much smaller [Ca2+] and phosphorylation transients, and stress development was slower. Peak [Ca2+] was proportional to the rate of stress development. Steady-state [Ca2+], phosphorylation, and stress values (which are dependent on extracellular Ca2+) were more sensitive to histamine concentration than was the peak [Ca2+] response both in the presence and absence of extracellular CaCl2 (measures of intracellular Ca2+ release). This result suggests that the mechanism for Ca2+ influx from the extracellular space is more sensitive to histamine than intracellular Ca2+ release. These results are also consistent with the hypothesis that agonist-releasable sarcoplasmic reticular Ca2+ is the major contributor to initial phosphorylation transients that enhance the rate of stress development.
Rembold
C M
CM
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Murphy
R A
RA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries; D006632:Histamine / Q000494:pharmacology*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D013552:Swine
D010656:Phenylephrine; D006632:Histamine; D009218:Myosins; D002118:Calcium