AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 4 646-G654, Copyright © 1990 by American Physiological Society
Effect of substance P and neurokinin A on rat parietal cell function
W. Schepp, J. Schmidtler, C. Tatge, V. Schusdziarra and M. Classen
Department of Internal Medicine II, Technical University of Munich, Federal Republic of Germany.
In enzymatically dispersed enriched (76%) rat parietal cells we studied the
effect of substance P on acid sequestration as indirectly measured by
[14C]aminopyrine accumulation. Substance P (10(-8)-10(-5) M) had no effect
on basal [14C]aminopyrine accumulation. Yet, the peptide reduced the
response to histamine and to the postreceptor agonists forskolin and
dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Inhibition by
substance P followed noncompetitive kinetics and reduced stimulated
parietal cell function by up to 45% at 10(-5) M. The antagonist [D-Pro2,
D-Trp7,9]-substance P at 10(-5) M partly reversed the inhibitory effect of
substance P. Cholinergic stimulation of [14C]aminopyrine accumulation was
not reduced by substance P. Neurokinin A, another tachykinin that is
structurally related to substance P, was of comparable potency and efficacy
in reducing [14C]aminopyrine accumulation in response to histamine,
forskolin, and DBcAMP. Inhibition of forskolin- or DBcAMP-induced
[14C]aminopyrine accumulation persisted in the presence of 10(-5) M
ranitidine. Inhibition by substance P and neurokinin A of the response to
histamine was not sensitive to pertussis toxin. Both tachykinins failed to
reduce histamine- and forskolin-stimulated cAMP production. Our data
suggest that substance P and neurokinin A exert a direct effect on rat
parietal cells. They attenuate histamine-stimulated acid sequestration at
an intracellular step that is distal to the adenylate cyclase and that does
not involve pertussis toxin-sensitive GTP-binding proteins.
