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 language | English (US) |
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Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 272 |
Issue number | 2 41-2 |
State | Published - Feb 1 1997 |
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)