| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL, USA
2 Department of Pharmacology and Anesthesiology, University of Illinois College of Medicine, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: rskidgel{at}uic.edu.
Kininase I-type carboxypeptidases convert native kinin agonists for B2 receptors into B1 receptor agonists by specifically removing the C-terminal Arg residue. The membrane localization of carboxypeptidase M (CPM) and CPD make them ideally situated to regulate kinin activity. Nitric oxide (NO) release from human lung microvascular endothelial cells (HLMVEC) was measured directly in real time with a porphyrinic microsensor. Bradykinin (1 - 100 nM) elicited a transient (5 min) peak of generation of NO that was blocked by the B2 antagonist HOE 140 whereas B1 agonist des-Arg10-kallidin caused a small linear increase in NO over 20 min. Treatment of HLMVEC with 5 ng/ml interleukin -1
and 200 U/ml interferon-
for 16 h upregulated B1 receptors as shown by an approximately 4-fold increase in prolonged (>20 min) output of NO in response to des-Arg10-kallidin, which was blocked by the B1 antagonist des-Arg10-Leu9-kallidin. B2 receptor agonists bradykinin or kallidin also generated prolonged NO production in treated HLMVEC, which was significantly reduced by either a B1 antagonist or carboxypeptidase inhibitor, and completely abolished with a combination of B1 and B2 receptor antagonists. Furthermore, CPM and CPD activities were increased about 2-fold in membrane fractions of HLMVEC treated with interleukin-1 and interferon- compared with control cells. Immunostaining localized CPD primarily in a perinuclear/Golgi region whereas CPM was on the cell membrane. These data show that cellular kininase I-type carboxypeptidases can enhance kinin signaling and NO production by converting B2 agonists to B1 agonists, especially in inflammatory conditions.
This article has been cited by other articles:
|
|
 |
|
  S. Helske, M. Laine, M. Kupari, J. Lommi, H. Turto, L. Nurmi, I. Tikkanen, K. Werkkala, K. A. Lindstedt, and P. T. Kovanen Increased expression of profibrotic neutral endopeptidase and bradykinin type 1 receptors in stenotic aortic valves Eur. Heart J., August 1, 2007; 28(15): 1894 - 1903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Hadkar, S. Sangsree, S. M. Vogel, V. Brovkovych, and R. A. Skidgel Carboxypeptidase-mediated enhancement of nitric oxide production in rat lungs and microvascular endothelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L35 - L45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Skidgel, F. Alhenc-Gelas, and W. B. Campbell Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Prologue: Kinins and related systems. New life for old discoveries Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1886 - H1891. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
