AJP - Cell Physiology, Vol 259, Issue 1 C150-C160, Copyright © 1990 by American Physiological Society
Effects of substance P on [Ca2+]i and force in intact guinea pig ileal smooth muscle
G. Matthijs, B. Himpens, T. L. Peeters and G. Vantrappen
Department of Medical Research, University of Leuven, Belgium.
In intact sheets of the guinea pig ileal longitudinal muscle, loaded with
fura-2, both substance P (SP)- and K(+)-induced contractile responses are
preceded by cytoplasmic free Ca2+ ([Ca2+]i) variations. In response to SP
(10(-10)-10(-7) M), [Ca2+]i and force increased concentration dependently.
From 10(-9) M on, the response was biphasic: an initial Ca2+ spike and
force transient were followed by a tonic component. The [Ca2+]i and force
vs. log [SP] curves were sigmoidal for the initial phasic component, while
a homologous receptor desensitization caused a reduced tonic component of
the [Ca2+]i and contractile response at higher concentrations of SP. Both
intracellular Ca2+ release and Ca2+ influx play a role in the effect of the
peptide. In depolarizing solutions (140 mM K+) and in Ca2(+)-free medium (2
mM EGTA), SP induced a transient increase in [Ca2+]i and force. The Ca2+
stores used by SP and acetylcholine (ACh) overlap. [Ca2+]i and force fell
to base-line levels when the extracellular Ca2+ was reduced from 1.2 to 0.2
mM during stimulation with SP. Verapamil reduced the tonic response. We
also studied the relation between [Ca2+]i and force for the peak and
steady-state values after stimulation with increasing concentrations of SP
and K+. The phasic force response was linearly related to log [Ca2+]i.
During the sustained response to K+, the Ca2+ sensitivity of the
contractile/regulatory proteins was decreased, whereas no changes were
observed during prolonged stimulation with the peptide.
