Abstract
The effects of the stable thromboxane analogue U46619, the α 1-adrenergic agent phenylephrine and depolarization with high K+ on cytoplasmic Ca2+ ([Ca2+]i) and force development were determined in rabbit pulmonary artery smooth muscle. Following stimulation with each of the excitatory agents, the time course of the [Ca2+]i/force relationship described counter-clockwise hysteresis loops with the rise and fall in [Ca2+]i leading, respectively, contraction and relaxation. The rank order of the force/[Ca2+]i ratios evoked by the different methods of stimulation was: U46619 > phenylephrine high K+. The difference between the actions of U46619 and phenylephrine was due to the lesser Ca2+-releasing and greater Ca2+-sensitizing action of U46619. Both U46619 and phenylephrine also released intracellular Ca2+ in intact (non-permeabilized) preparations. The effects of the two agonists on force, at constant free cytoplasmic [Ca2+] maintained with EGTA, were also determined in preparations permeabilized with staphylococcal α-toxin, in which intracellularly stored Ca2+ was eliminated with A23187. Sensitization of the contractile response to Ca2+ by agonists was indicated by the contractile responses of permeabilized muscles to U46619 and to phenylephrine, in the presence of constant, highly buffered [Ca2+]i. These contractions were inhibited by GDP[βS] and could also be elicited by GTP. We conclude that, in addition to changing [Ca2+]i, pharmacomechanical coupling can also modulate contraction by altering the sensitivity of the regulatory/contractile apparatus of smooth muscle to [Ca2+]i, through a G-protein-coupled mechanism.
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Himpens, B., Kitazawa, T. & Somlyo, A.P. Agonist-dependent modulation of Ca2+ sensitivity in rabbit pulmonary artery smooth muscle. Pflugers Arch. 417, 21–28 (1990). https://doi.org/10.1007/BF00370764
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DOI: https://doi.org/10.1007/BF00370764