Canine pulmonary vasoreactivity to serotonin

Role of protein kinase C and tyrosine kinase

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15 Citations (Scopus)

Abstract

The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10-5 M) significantly increased precapillary resistance by ~150% and postcapillary resistance twofold and significantly decreased total vascular compliance to ~50% of control values by decreasing large- vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10-7 M), the protein kinase C inhibitor staurosporine (10-7 M), the voltage-dependent Ca2+-channel blocker verapamil (10-5 M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10- 4 M) and tyrphostin 25 (5 x 10-4 M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10-7 M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number2 41-2
StatePublished - Feb 1 1997

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Protein-Tyrosine Kinases
Canidae
Serotonin
Compliance
Blood Vessels
Lung
Protein Kinase Inhibitors
Protein Kinase C
Signal Transduction
Serotonin 5-HT1 Receptors
Serotonin 5-HT1 Receptor Antagonists
Pindolol
Ketanserin
Staurosporine
Protein C Inhibitor
Genistein
Verapamil
Vascular Resistance
Tyrosine
protein kinase C kinase

Keywords

  • genistein
  • ketanserin
  • pulmonary capillary pressure
  • pulmonary vascular compliance
  • pulmonary vascular resistance
  • staurosporine
  • tyrphostin 25
  • vasoconstriction
  • verapamil
  • voltage-dependent calcium channels

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Canine pulmonary vasoreactivity to serotonin: Role of protein kinase C and tyrosine kinase",
abstract = "The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10-5 M) significantly increased precapillary resistance by ~150{\%} and postcapillary resistance twofold and significantly decreased total vascular compliance to ~50{\%} of control values by decreasing large- vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10-7 M), the protein kinase C inhibitor staurosporine (10-7 M), the voltage-dependent Ca2+-channel blocker verapamil (10-5 M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10- 4 M) and tyrphostin 25 (5 x 10-4 M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10-7 M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.",
keywords = "genistein, ketanserin, pulmonary capillary pressure, pulmonary vascular compliance, pulmonary vascular resistance, staurosporine, tyrphostin 25, vasoconstriction, verapamil, voltage-dependent calcium channels",
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T2 - Role of protein kinase C and tyrosine kinase

AU - Barman, Scott A.

AU - Pauly, James R.

AU - Isales, Carlos M.

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N2 - The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10-5 M) significantly increased precapillary resistance by ~150% and postcapillary resistance twofold and significantly decreased total vascular compliance to ~50% of control values by decreasing large- vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10-7 M), the protein kinase C inhibitor staurosporine (10-7 M), the voltage-dependent Ca2+-channel blocker verapamil (10-5 M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10- 4 M) and tyrphostin 25 (5 x 10-4 M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10-7 M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

AB - The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10-5 M) significantly increased precapillary resistance by ~150% and postcapillary resistance twofold and significantly decreased total vascular compliance to ~50% of control values by decreasing large- vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10-7 M), the protein kinase C inhibitor staurosporine (10-7 M), the voltage-dependent Ca2+-channel blocker verapamil (10-5 M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10- 4 M) and tyrphostin 25 (5 x 10-4 M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10-7 M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

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KW - voltage-dependent calcium channels

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