![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
GH Caughey, F Leidig, NF Viro and JA Nadel
Cardiovascular Research Institute, University of California, San Francisco.
The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.
This article has been cited by other articles:
|
|
 |
|
  X.-Z. Shi and S. K. Sarna Gene therapy of Cav1.2 channel with VIP and VIP receptor agonists and antagonists: a novel approach to designing promotility and antimotility agents Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G187 - G196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. H. Caughey, J. Beauchamp, D. Schlatter, W. W. Raymond, N. N. Trivedi, D. Banner, H. Mauser, and J. Fingerle Guinea Pig Chymase Is Leucine-specific: A NOVEL EXAMPLE OF FUNCTIONAL PLASTICITY IN THE CHYMASE/GRANZYME FAMILY OF SERINE PEPTIDASES J. Biol. Chem., May 16, 2008; 283(20): 13943 - 13951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Canning Reflex regulation of airway smooth muscle tone J Appl Physiol, September 1, 2006; 101(3): 971 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Schiemann, T. A. Grimm, J. Hoch, R. Gross, B. Lindner, F. Petersen, S. Bulfone-Paus, and E. Brandt Mast cells and neutrophils proteolytically activate chemokine precursor CTAP-III and are subject to counterregulation by PF-4 through inhibition of chymase and cathepsin G Blood, March 15, 2006; 107(6): 2234 - 2242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Karlson, G. Pejler, B. Tomasini-Johansson, and L. Hellman Extended Substrate Specificity of Rat Mast Cell Protease 5, a Rodent {alpha}-Chymase with Elastase-like Primary Specificity J. Biol. Chem., October 10, 2003; 278(41): 39625 - 39631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Walsh MAST CELLSAND ORAL INFLAMMATION Crit. Rev. Oral. Biol. Med., May 1, 2003; 14(3): 188 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Temkin, B. Kantor, V. Weg, M.-L. Hartman, and F. Levi-Schaffer Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release J. Immunol., September 1, 2002; 169(5): 2662 - 2669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. KONDO, S. KAGAMI, H. KIDO, F. STRUTZ, G. A. MULLER, and Y. KURODA Role of Mast Cell Tryptase in Renal Interstitial Fibrosis J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1668 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Miyazaki and S. Takai Role of chymase on vascular proliferation Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1): 23 - 26. [PDF]
|
|
|
|
|
|
A. Rydning, O. Lyng, S. Aase, and J. E. Gronbech Substance P may attenuate gastric hyperemia by a mast cell-dependent mechanism in the damaged gastric mucosa Am J Physiol Gastrointest Liver Physiol, November 1, 1999; 277(5): G1064 - G1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takai, D. Jin, M. Sakaguchi, and M. Miyazaki Chymase-Dependent Angiotensin II Formation in Human Vascular Tissue Circulation, August 10, 1999; 100(6): 654 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, Y. Li, S. W. Reddel, M. Cherrian, D. S. Friend, R. L. Stevens, and S. A. Krilis Identification of Basophilic Cells that Express Mast Cell Granule Proteases in the Peripheral Blood of Asthma, Allergy, and Drug-Reactive Patients J. Immunol., November 1, 1998; 161(9): 5079 - 5086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gololobov, Y. Noda, S. Sherman, I. Rubinstein, J. Baranowska-Kortylewicz, and S. Paul Stabilization of Vasoactive Intestinal Peptide by Lipids J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 753 - 758. [Abstract] [Full Text]
|
|
|
|
|
|
D. C. Thompson and R. J. Altiere Differential Susceptibility of Tracheal Contraction to Nonadrenergic Noncholinergic Relaxation J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 19 - 24. [Abstract] [Full Text]
|
|
|
|
|
|
C. Huang, G. W. Wong, N. Ghildyal, M. F. Gurish, A. Sali, R. Matsumoto, W.-T. Qiu, and R. L. Stevens The Tryptase, Mouse Mast Cell Protease 7, Exhibits Anticoagulant Activity in Vivo and in Vitro Due to Its Ability to Degrade Fibrinogen in the Presence of the Diverse Array of Protease Inhibitors in Plasma J. Biol. Chem., December 12, 1997; 272(50): 31885 - 31893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. MIURA, H. YAMAUCHI, M. ICHINOSE, Y. OHUCHI, N. KAGEYAMA, M. TOMAKI, N. ENDOH, and K. SHIRATO Impairment of Neural Nitric Oxide-mediated Relaxation after Antigen Exposure in Guinea Pig Airways in vitro Am. J. Respir. Crit. Care Med., July 1, 1997; 156(1): 217 - 222. [Abstract] [Full Text]
|
|
|
|
|
|
K. C. ELROD, W. R. MOORE, W. M. ABRAHAM, and R. D. TANAKA Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 375 - 381. [Abstract] [Full Text]
|
|
|
|
|
|
S. Sanker, U. M. Chandrasekharan, D. Wilk, M. J. Glynias, S. S. Karnik, and A. Husain Distinct Multisite Synergistic Interactions Determine Substrate Specificities of Human Chymase and Rat Chymase-1 for Angiotensin II Formation and Degradation J. Biol. Chem., January 31, 1997; 272(5): 2963 - 2968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Bagarozzi Jr., R. Pike, J. Potempa, and J. Travis Purification and Characterization of a Novel Endopeptidase in Ragweed (Ambrosia artemisiifolia) Pollen J. Biol. Chem., October 18, 1996; 271(42): 26227 - 26232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Hunt, R. L. Stevens, K. F. Austen, J. Zhang, Z. Xia, and N. Ghildyal Natural Disruption of the Mouse Mast Cell Protease 7 Gene in the C57BL/6 Mouse J. Biol. Chem., February 2, 1996; 271(5): 2851 - 2855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Raymond, E. K. Tam, J. L. Blount, and G. H. Caughey Purification and Characterization of Dog Mast Cell Protease-3, an Oligomeric Relative of Tryptases J. Biol. Chem., June 2, 1995; 270(22): 13164 - 13170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-H. Jeohn and K. Takahashi Purification and Characterization of a Vasoactive Intestinal Polypeptide-degrading Endoprotease from Porcine Antral Mucosal Membranes J. Biol. Chem., April 7, 1995; 270(14): 7809 - 7815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, S. S. Karnik, and A. Husain Human Prochymase Activation J. Biol. Chem., February 3, 1995; 270(5): 2218 - 2223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Paul, D. Volle, C. Beach, D. Johnson, M. Powell, and R. Massey Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody Science, June 9, 1989; 244(4909): 1158 - 1162. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
