Article date: October 1991
By: Anant B. Parekh, Alison F. Brading, in Volume 104, Issue 2, pages 412-418
The action of carbachol on the mechanical activity of circular muscle from guinea‐pig upper stomach was studied. High concentrations of carbachol (e.g. 10−4m) produced a rapid phasic contraction followed by a smaller, sustained tonic contraction. Low concentrations (e.g. 10−7m) caused a contraction which did not generally show marked distinction between phasic and tonic components.
The response to 10−7m carbachol was very sensitive to 10−5m nifedipine as was the phasic response to 10−4m carbachol. The tonic contraction to the latter, however, was only slightly reduced by nifedipine.
The carbachol‐induced contractions remaining in the presence of nifedipine were dose‐related and very dependent on the presence of external calcium.
Carbachol, 10−7m, did not produce a contraction after 4 min exposure to calcium‐free solution whereas 10−4m carbachol did and this was phasic in nature but much reduced relative to the control in normal Ca.
A phasic followed by a small tonic contraction to 10−4m carbachol was seen superimposed on the K contracture in tissues depolarized with 100 mm K, whereas only a small tonic response occurred for 10−7m carbachol.
In the absence of a functional carbachol‐sensitive intracellular store, 10−4m carbachol was unable to trigger a contraction in calcium‐free solution. However, when calcium was simultaneously readmitted with carbachol after exposure to calcium‐free solution, a contraction occurred.
Carbachol, 10−7m, did not significantly increase inositol polyphosphate levels, whereas 10−4m carbachol did. The increase with 10−4m occurred rapidly peaking within 2 min and was undetectable after 5 min, in the absence of lithium.
It is concluded that low concentrations of muscarinic agonist trigger a contraction predominantly through a nifedipine‐sensitive route whereas higher concentrations further utilize intracellular calcium release and a receptor‐operated extracellular calcium‐dependent pathway. The former is probably associated with the phasic component and the latter with the tonic one.
The action of carbachol on the mechanical activity of circular muscle from guinea‐pig upper stomach was studied. High concentrations of carbachol (e.g. 10−4m) produced a rapid phasic contraction followed by a smaller, sustained tonic contraction. Low concentrations (e.g. 10−7m) caused a contraction which did not generally show marked distinction between phasic and tonic components.
The response to 10−7m carbachol was very sensitive to 10−5m nifedipine as was the phasic response to 10−4m carbachol. The tonic contraction to the latter, however, was only slightly reduced by nifedipine.
The carbachol‐induced contractions remaining in the presence of nifedipine were dose‐related and very dependent on the presence of external calcium.
Carbachol, 10−7m, did not produce a contraction after 4 min exposure to calcium‐free solution whereas 10−4m carbachol did and this was phasic in nature but much reduced relative to the control in normal Ca.
A phasic followed by a small tonic contraction to 10−4m carbachol was seen superimposed on the K contracture in tissues depolarized with 100 mm K, whereas only a small tonic response occurred for 10−7m carbachol.
In the absence of a functional carbachol‐sensitive intracellular store, 10−4m carbachol was unable to trigger a contraction in calcium‐free solution. However, when calcium was simultaneously readmitted with carbachol after exposure to calcium‐free solution, a contraction occurred.
Carbachol, 10−7m, did not significantly increase inositol polyphosphate levels, whereas 10−4m carbachol did. The increase with 10−4m occurred rapidly peaking within 2 min and was undetectable after 5 min, in the absence of lithium.
It is concluded that low concentrations of muscarinic agonist trigger a contraction predominantly through a nifedipine‐sensitive route whereas higher concentrations further utilize intracellular calcium release and a receptor‐operated extracellular calcium‐dependent pathway. The former is probably associated with the phasic component and the latter with the tonic one.
DOI: 10.1111/j.1476-5381.1991.tb12444.x
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