Temperature and histamine receptor function—what is really happening?

1985 ◽  
Vol 63 (6) ◽  
pp. 751-755 ◽  
Author(s):  
D. A. Cook ◽  
C. A. Krueger ◽  
A. Michalchuk

Early studies suggested that at low temperatures there was a transition of receptor type from an H1 to an H2 receptor when the temperature was reduced from 37 °C to temperatures below 20 °C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2 antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1–H2 receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested.

2007 ◽  
Vol 292 (3) ◽  
pp. G887-G898 ◽  
Author(s):  
Daniel P. Poole ◽  
John B. Furness

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.


Sign in / Sign up

Export Citation Format

Share Document