Effect of Modulators of Tyrosine Kinase Activity on Agonist-induced Contraction in the Rat Pulmonary Vascular Smooth Muscle

Savineau, Jean‐Pierre; Fuente, Patrick Gonzalez De La; Marthan, Roger

doi:10.1006/pulp.1996.0022

Cited by 16 publications

(10 citation statements)

References 6 publications

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“…In a number of cell types (Parekh and Penner 1997), including smooth muscle (Burt et al 1995;Savineau et al 1996), it has been suggested that the link between store depletion and the opening of SOCs involves a tyrosine kinase step; most commonly, such experiments have involved the use of an inhibitor of tyrosine kinase such as genistein. In the present study, genistein was found to reduce the verapamil-resistant components of both the contraction and calcium influx observed in the presence of Tg, which would be consistent with a role for tyrosine kinase in capacitative calcium entry in the mouse anococcygeus.…”

Section: Discussionmentioning

confidence: 99%

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Wallace

Ayman

McFadzean

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The sarcoplasmic reticulum Ca-ATPase inhibitor thapsigargin (Tg; 0.4-100 nM) produced concentration-related, strong and sustained contractions of the mouse-isolated anococcygeus muscle; these contractions were dependent on extracellular calcium but were only partially reduced (by about 50%) in the presence of verapamil (10 and 100 microM). The verapamil-resistant component of the Tg-induced contraction was relaxed by the general calcium entry blockers SKF96365 (0.4-40 microM) and cadmium (50-300 microM), and by the tyrosine kinase inhibitor genistein (10-180 microM). In single smooth muscle cells loaded with Fura-2, addition of Tg (100 nM) to calcium-free medium produced a small, transient increase in fluorescence; subsequent addition of calcium (2.5 mM) produced a larger and sustained increase which was abolished on return to calcium-free conditions, but was only partially reduced by verapamil (10 microM; by about 30%). Manganese quenching of Fura-2 was enhanced in cells treated with Tg. The verapamil-resistant calcium influx was reduced by SKF96365 (20 microM) and to a lesser extent by genistein (40 microM); cadmium (200 microM) produced an initial decrease in fluorescence followed by a marked increase. These results demonstrate that, in the mouse anococcygeus, Tg can cause sustained contractions and elevations of calcium influx in the presence of verapamil; the time-course, calcium dependence and, although to a lesser extent, pharmacology of these effects generally support the proposal that excitation-contraction coupling in this tonic smooth muscle involves sustained capacitative calcium influx.

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Section: Discussionmentioning

confidence: 99%

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Wallace

Ayman

McFadzean

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In contrast, others demonstrated that the vasoconstrictor response to norepinephrine in the feline pulmonary vascular bed was attenuated by PKC inhibitors (22) and likely mediated by Ca 2ϩ -independent PKC-␦ isozyme/calmodulin-dependent kinase III (5). Others suggested that the contractile response to norepinephrine in isolated rat pulmonary artery is largely mediated by TK activation (42). In none of these studies were [Ca 2ϩ ] i and tension simultaneously measured in the same tissue so that the role of PKC, TK, or ROK in [Ca 2ϩ ] i and myofilament Ca 2ϩ sensitivity in response to ␣-adrenoreceptor activation could be adequately assessed.…”

mentioning

confidence: 99%

“…Sensitization of the contractile apparatus to Ca 2ϩ appears to be one important mechanism of pharmacomechanical coupling (12). Activation of PKC (4,5,11,22), tyrosine kinases (TK) (7,18,19,42), and/or Rho kinase (ROK) (18,46) have been suggested to play important roles in the signal transduction events associated with vascular smooth muscle contraction. However, the relative roles of PKC, TK, and ROK in regulating [Ca 2ϩ ] i , myofilament Ca 2ϩ sensitivity, and tension in response to ␣-adrenoreceptor stimulation have not been fully elucidated.…”

mentioning

confidence: 99%

Role of PKC, tyrosine kinases, and Rho kinase in α-adrenoreceptor-mediated PASM contraction

Damron

Kanaya

Homma

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Our objectives were to identify the relative contributions of intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in the pulmonary artery smooth muscle (PASM) contractile response to the alpha-adrenoreceptor agonist phenylephrine (PE) and to assess the role of PKC, tyrosine kinases (TK), and Rho kinase (ROK) in that response. Our hypothesis was that multiple signaling pathways are involved in the regulation of [Ca2+]i, myofilament Ca2+ sensitization, and vasomotor tone in response to alpha-adrenoreceptor stimulation of PASM. Simultaneous measurement of [Ca2+]i and isometric tension was performed in isolated canine pulmonary arterial strips loaded with fura 2-AM. PE-induced tension development was due to sarcolemmal Ca2+ influx, Ca2+ release from inositol 1,4,5-trisphosphate-dependent sarcoplasmic reticulum Ca2+ stores, and myofilament Ca2+ sensitization. Inhibition of either PKC or TK partially attenuated the sarcolemmal Ca2+ influx component and the myofilament Ca2+ sensitizing effect of PE. Combined inhibition of PKC and TK did not have an additive attenuating effect on PE-induced Ca2+ sensitization. ROK inhibition slightly decreased [Ca2+]i but completely inhibited myofilament Ca2+ sensitization. These results indicate that PKC and TK activation positively regulate sarcolemmal Ca2+ influx in response to alpha-adrenoreceptor stimulation in PASM but have relatively minor effects on myofilament Ca2+ sensitivity. ROK is the predominant pathway mediating PE-induced myofilament Ca2+ sensitization.

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“…On the other hand, it has been reported that the tyrosine kinase inhibitors, genistein and tyrphostin, decreased agonist‐induced contraction in various tissues of different species, thereby suggesting that tyrosine phosphorylation of some proteins may play a role in agonist‐induced contraction [10,18,28–30].…”

Section: Discussionmentioning

confidence: 99%

Tyrosine kinase participates in vasoconstriction through a Ca²⁺‐ and myosin light chain phosphorylation‐independent pathway

et al. 2002

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Effect of Modulators of Tyrosine Kinase Activity on Agonist-induced Contraction in the Rat Pulmonary Vascular Smooth Muscle

Cited by 16 publications

References 6 publications

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Role of PKC, tyrosine kinases, and Rho kinase in α-adrenoreceptor-mediated PASM contraction

Tyrosine kinase participates in vasoconstriction through a Ca²⁺‐ and myosin light chain phosphorylation‐independent pathway

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Effect of Modulators of Tyrosine Kinase Activity on Agonist-induced Contraction in the Rat Pulmonary Vascular Smooth Muscle

Cited by 16 publications

References 6 publications

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Thapsigargin-induced tone and capacitative calcium influx in mouse anococcygeus smooth muscle cells

Role of PKC, tyrosine kinases, and Rho kinase in α-adrenoreceptor-mediated PASM contraction

Tyrosine kinase participates in vasoconstriction through a Ca2+‐ and myosin light chain phosphorylation‐independent pathway

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Tyrosine kinase participates in vasoconstriction through a Ca²⁺‐ and myosin light chain phosphorylation‐independent pathway