Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

1990 ◽  
Vol 46 (10) ◽  
pp. 1037-1041 ◽  
Author(s):  
A. Rakovska ◽  
K. Milenov ◽  
P. Henklein
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Guinea Pig Ileum ◽  
Cholecystokinin Antagonist

PKC δ-isoform translocation and enhancement of tonic contractions of gastrointestinal smooth muscle

2007 ◽  
Vol 292 (3) ◽  
pp. G887-G898 ◽  
Author(s):  
Daniel P. Poole ◽  
John B. Furness
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Specific Inhibitor ◽  
Smooth Muscle Contraction ◽  
Enteric Neurons ◽  
Guinea Pig Ileum ◽  
Tonic Component ◽  
Gastrointestinal Smooth Muscle ◽  
Immunohistochemical Evidence

PKC is involved in mediating the tonic component of gastrointestinal smooth muscle contraction in response to stimulation by agonists for G protein-coupled receptors. Here, we present pharmacological and immunohistochemical evidence indicating that a member of the novel PKC isoforms, PKC-δ, is involved in maintaining muscarinic receptor-coupled tonic contractions of the guinea pig ileum. The tonic component of carbachol-evoked contractions was enhanced by an activator of conventional and novel PKCs, phorbol 12,13-dibutyrate (PDBu; 200 nM or 1 μM), and by an activator of novel PKCs, ingenol 3,20-dibenzoate (IDB; 100 or 500 nM). Enhancement was unaffected by concentrations of bisindolylmaleimide I (BIM-I; 22 nM) that block conventional PKCs or by a PKC-ε-specific inhibitor peptide but was attenuated by higher doses of BIM-I (2.2 μM). Relevant proteins were localized at a cellular and subcellular level using confocal analysis. Immunohistochemical staining of the ileum showed that PKC-δ was exclusively expressed in smooth muscles distributed throughout the layers of the gut wall. PKC-ε immunoreactivity was prominent in enteric neurons but was largely absent from smooth muscle of the muscularis externa. Treatment with PDBu, IDB, or carbachol resulted in a time- and concentration-dependent translocation of PKC-δ from the cytoplasm to filamentous structures within smooth muscle cells. These were parallel to, but distinct from, actin filaments. The translocation of PKC-δ in response to carbachol was significantly reduced by scopolamine or calphostin C. The present study indicates that the tonic carbachol-induced contraction of the guinea pig ileum is mediated through a novel PKC, probably PKC-δ.

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