|
|
||||||||
Department of Medicine, Rhode Island Hospital, and Brown University School of Medicine, Providence, Rhode Island 02903
The signal transduction that mediates
CCK-induced contraction of gallbladder muscle was investigated in the
cat. Contraction was measured by scanning micrometry in single muscle
cells isolated enzymatically with collagenase. Production of
D-myo-inositol
1,4,5-trisphosphate (IP3) and
sn-1,2-diacylglycerol (DAG) was
quantitated using HPLC and TLC, respectively. Protein kinase C (PKC)
activity was determined by measuring the phosphorylation of a specific
substrate peptide from myelin basic protein, Ac-MBP-(4
14).
CCK-induced contraction was blocked by incubation in strontium medium,
pertussis toxin (PTx), and antibodies against
Gi
3
or 
-subunits but was not blocked by
Ca2+-free medium or by antibodies
against Gq/11
,
Gi
1-2,
or Go
. The contraction induced
by CCK was inhibited by the phospholipase C (PLC) inhibitor U-73122,
anti-PLC-
3 antibody, and the
IP3 receptor antagonist heparin
but was not inhibited by the the phospholipase D inhibitor propranolol
or antibodies against PLC-
1 or PLC-
2. Western blot analysis of
gallbladder muscle revealed the presence of PLC-
2 and PLC-
3 but
not PLC-
1. CCK caused a 94% increase in
IP3 generation and an 86%
increase in DAG generation. A low dose of CCK caused PKC translocation,
and CCK-induced contraction was blocked by the PKC inhibitor H-7. A
high dose of CCK, however, caused no PKC translocation, and its
contraction was blocked by the calmodulin antagonist CGS9343B. In
conclusion, CCK contracts cat gallbladder muscle by stimulating
PTx-sensitive Gi 3 protein coupled with PLC-
3, producing
IP3 and DAG. Low doses activate PKC, whereas high doses activate calmodulin.
G proteins; phospholipase C; inositol 1,4,5-trisphosphate; protein kinase C
This article has been cited by other articles:
![]() |
O. B. Balemba, T. J. Heppner, A. D. Bonev, M. T. Nelson, and G. M. Mawe Calcium waves in intact guinea pig gallbladder smooth muscle cells Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G717 - G727. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Dufresne, C. Seva, and D. Fourmy Cholecystokinin and gastrin receptors. Physiol Rev, July 1, 2006; 86(3): 805 - 847. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z.-L. Xiao, W. Cao, P. Biancani, and J. Behar Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): 1008 - 1015. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. B. Balemba, M. J. Salter, T. J. Heppner, A. D. Bonev, M. T. Nelson, and G. M. Mawe Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G655 - G664. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Morales, P. J. Camello, G. M. Mawe, and M. J. Pozo Characterization of intracellular Ca2+ stores in gallbladder smooth muscle Am J Physiol Gastrointest Liver Physiol, March 1, 2005; 288(3): G507 - G513. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Morales, P. J. Camello, S. Alcon, G. M. Salido, G. Mawe, and M. J. Pozo Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder Am J Physiol Gastrointest Liver Physiol, June 1, 2004; 286(6): G1090 - G1100. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. L. Guarino, Z.-L. Xiao, P. Biancani, and J. Behar PAF-like lipids- and PAF-induced gallbladder muscle contraction is mediated by different pathways in guinea pigs Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1189 - G1197. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Sarna Neuronal locus and cellular signaling for stimulation of ileal giant migrating and phasic contractions Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G789 - G797. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Y. Shin, Y. P. Lee, T. S. Lee, H. D. Je, D. S. Kim, and U. D. Sohn The Signal Transduction of Endothelin-1-Induced Circular Smooth Muscle Cell Contraction in Cat Esophagus J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 924 - 934. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Piiper, R. Gebhardt, B. Kronenberger, C. D. Giannini, R. Elez, and S. Zeuzem Pertussis Toxin Inhibits Cholecystokinin- and Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Activation by Disinhibition of the cAMP Signaling Pathway and Inhibition of c-Raf-1 Mol. Pharmacol., September 1, 2000; 58(3): 608 - 613. [Abstract] [Full Text] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |