ISSN:
1474-8673
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Chemie und Pharmazie
,
Medizin
Notizen:
1 In the present investigation we examined the regulation of calmodulin (CaM)- and protein kinase C (PKC)-dependent pathways by cytosolic Ca2+ in the contraction of cat lower oesophageal sphincter (LES). 2 Force developed in response to increasing doses of acetylcholine (ACh) was directly related to the increase of the [Ca2+]i measured by fura-2. Thapsigargin, which depletes Ca2+ stores, reduced the contraction and the [Ca2+]i. In addition, contraction in response to maximal ACh was reduced by the CaM inhibitor CGS9343B but not by the PKC inhibitor chelerythrine. The contraction in response to submaximal ACh was reduced by chelerythrine but not by CGS9343B. 3 In permeabilized cells, the contraction in response to low Ca2+ (0.54 μm) was also reduced by CGS9343B. 4 The response to high Ca2+ (1.0 μm) was reduced by CGS9343B. ACh also inhibited PKC activation induced by diacylglycerol, which activation is inhibited by the N-myristoylated peptide inhibitor derived from pseudosubstrate sequences of PKCαβγ (myr-PKC-αβγ), but not of myr-PKC-α. 5 These data are consistent with the view that activated CaM-dependent pathways inhibit PKC-dependent pathways, this switch mechanism might be regulated by Ca2+ in the LES.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1474-8673.2004.00302.x
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