Classical second messengers are not involved in proteinase-induced
degranulation of airway gland serous cells.
Sommerhoff, Christian P., Kenneth C. Fang, Jay A. Nadel, and George H.
Caughey.
Cardiovascular Research Institute and Departments of Medicine and
Physiology, University of California San Francisco, San Francisco, CA
94143-0130
APStracts 3:0115L, 1996.
Neutral serine proteinases such as mast cell chymase, cathepsin G, and
neutrophil elastase are far more potent secretagogues for airway
gland serous cells than all other agonists studied (e.g., histamine
and bradykinin). To determine the mechanism of proteinase-induced
secretion, we investigated the stimulation-secretion coupling in
cultured bovine serous cells. Histamine stimulates degranulation of
serous cells via cAMP-, protein kinase C-, and [Ca2+]i-dependent
pathways. Similarly, bradykinin-induced secretion involves inositol
phosphates, protein kinaseEC, and [Ca2+]i. Degranulation caused by
both agonists also depends on the activity of an endogenous
metalloprotease which is required in a late step of stimulation
-secretion coupling, i.e. after the calcium entry. Based on the effect
of different inhibitors, this metalloprotease is a Zn2+- and Ca2+
-dependent enzyme similar to a gelatinase A synthesised by serous
cells. In marked contrast to other secretagogues, degranulation
induced by chymase, cathepsin G, and neutrophil elastase neither
involves the classical second messen gers nor the activity of the
endogenous metalloprotease. These observations suggest that exogenous
proteinases like chymase, cathepsin G and elastase may substitute for
or mimic the action of an endogenous metalloprotease and directly
activate degranulation, bypassing the signal transduction mechanisms
necessary for secretion caused by other agonists.
Received 14 February 1995; accepted in final form 10 June 1996.
APS Manuscript Number L45-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996