IngentaConnect Differential regulation by Ca2+ of calmodulin- and PKC-dependent ...

Authors: Sohn, U. D.¹; Park, J. H.¹; Lee, T. S.¹; Shin, C. Y.¹; Jeong, J. H.¹; Kim, J. H.¹; Je, H. D.¹; Dartt, D. A.²; Zoukhri, D.²; Choi, H. C.³; Lee, K. Y.³

Source: Autonomic & Autacoid Pharmacology, Volume 23, Numbers 5-6, October 2003 , pp. 307-317(11)

Publisher: Blackwell Publishing

Abstract:

Summary

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 m) was also reduced by CGS9343B.

4 The response to high Ca²⁺ (1.0 m) 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 PKC (myr-PKC-), but not of myr-PKC-.

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.

Keywords: Ca2+; CaM; PKC; lower oesophageal sphincter

Document Type: Research article

DOI: 10.1111/j.1474-8673.2004.00302.x

Affiliations: 1: Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea 2: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA 3: Department of Pharmacology, Yeungnam Medical School, Taegu 705-035, Korea

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Differential regulation by Ca2+ of calmodulin- and PKC-dependent contractile pathways in cat lower oesophageal sphincter

Differential regulation by Ca²⁺ of calmodulin- and PKC-dependent contractile pathways in cat lower oesophageal sphincter