Journal of Applied Physiology, Vol 70, Issue 2 813-817, Copyright © 1991 by American Physiological Society
Substance P-induced contraction of rabbit airways: mechanism of action
C. L. Armour, P. R. Johnson, L. A. Alouan and J. L. Black
Department of Pharmacy, University of Sydney, New South Wales, Australia.
The mechanism by which substance P induces contraction of airway smooth
muscle has been the subject of numerous reports. It has been suggested that
in rabbit airways the action of substance P is indirect, via the release of
endogenous acetylcholine, whereas this is not so in other species. The
present detailed study investigated whether substance P-induced contraction
in rabbit isolated bronchus and trachea is due to the release of endogenous
acetylcholine or in bronchus is due to histamine release and whether
substance P is metabolized by the enzymes enkephalinase and
acetylcholinesterase. Isometric contraction to cumulative addition of
substance P was measured in the presence of 10(-6) and 10(-4) M atropine,
10(-6) M pyrilamine, 10(-5) M phosphoramidon, or 3 x 10(-7) M neostigmine.
Neither atropine nor pyrilamine had any effect on the substance P
responses. Phosphoramidon, however, produced a 12-fold shift to the left in
the response curve with a decrease in the 50% effective concentration from
7.0 x 10(-8) to 6.1 x 10(-9) M (n = 4 control and 5 treated; P less than
0.05). In contrast, neostigmine at a concentration that produced a sixfold
shift to the left in the acetylcholine response curve had no effect on
substance P responses. We conclude that, in rabbit airways in vitro,
substance P-induced contraction is not mediated by release of endogenous
acetylcholine or histamine. In addition, endogenous enkephalinase but not
acetylcholinesterase may be involved in the degradation of substance P. Our
results show that, in contrast to previous studies in rabbits, the
mechanism of action of substance P may resemble that described in humans.
