PMID- 16954694
OWN - NLM
STAT- MEDLINE
DCOM- 20061221
LR  - 20131121
IS  - 0012-2823 (Print)
IS  - 0012-2823 (Linking)
VI  - 73
IP  - 4
DP  - 2006
TI  - Signal transduction pathways mediating CCK-8S-induced gastric antral smooth 
      muscle contraction.
PG  - 249-58
AB  - AIM: To investigate the functional and molecular mechanisms by which sulfated 
      cholecystokinin octapeptide (CCK-8S) regulates calcium mobilization in gastric 
      antral smooth muscle cells (SMCs) of rats. METHODS: Isotonic contraction of 
      antral strips was recorded using a polyphysiograph. Immunoprecipitation was used 
      to determine the regulatory effect of protein kinase C (PKC) on regulating the 
      phosphorylation of the type III inositol 1,4,5-triphosphate receptor (InsP(3)R3) 
      in gastric SMCs. Alterations in the intracellular calcium ([Ca(2+)](i)) 
      concentration were assayed using fura-2/AM-loaded microspectrofluorometry, and 
      the L-type calcium current (I(Ca-L)) was recorded by patch-clamp techniques. 
      RESULTS: CCK-8S (5 x 10(-8) mol/l) significantly increased the mean contractile 
      amplitude of circular muscle by 61.85 +/- 12.67% and the frequency of 
      longitudinal muscle by 57.91 +/- 15.70% in gastric antral strips, which were 
      suppressed by dexloxiglumide or thapsigargin (TG) and BAPTA-AM (BA). Treatment 
      with chelerythrine (5 x 10(-8) mmol/l) significantly inhibited the 
      CCK-8S-increased phosphorylation of InsP(3)R3 in SMCs. The amplitudes of the 
      CCK-8S-triggered [Ca(2+)](i) concentration oscillations were reduced in a 
      dose-dependent manner when the SMCs were pretreated with increasing 
      concentrations of PMA (from 10(-8) to 10(-5) mol/l). On removal of extracellular 
      calcium or blocking I(Ca-L) by nifedipine, a smaller but significant rise in the 
      [Ca(2+)](i) concentration was still elicited by CCK-8S. When [Ca(2+)](i) was 
      depleted by the administration of 10(-5) mol/l TG and 10(-5) mol/l BA or blocked 
      by the calcium-dependent chloride current (I(Cl-Ca)) by giving 5 x 10(-6) mol/l 
      niflumic acid, the CCK-8S-intensified I(Ca-L) (from -56.42 +/- 6.57 to -88.54 +/- 
      5.71 pA) was apparently inhibited by 90.34 +/- 4.71% and 82.59 +/- 4.24%. 
      CONCLUSIONS: These results demonstrate that the CCK-8S-evoked [Ca(2+)](i) 
      concentration increase in gastric antral SMCs depends on the release of 
      [Ca(2+)](i) stores which are negatively regulated by PKC-mediated phosphorylation 
      of InsP(3)R3. Released calcium in turn activates I(Ca-L) through the activation 
      of I(Cl-Ca), ultimately resulting in the contraction of the gastric smooth 
      muscle.
CI  - Copyright (c) 2006 S. Karger AG, Basel.
FAU - Si, Xin-Min
AU  - Si XM
AD  - Department of Digestive Medicine, Renmin Hospital, Wuhan University, 238 Jiefang 
      Road, Hubei 430060, China.
FAU - Huang, Lei
AU  - Huang L
FAU - Paul, Shelley Chireyath
AU  - Paul SC
FAU - An, Ping
AU  - An P
FAU - Luo, He-Sheng
AU  - Luo HS
LA  - eng
PT  - Journal Article
DEP - 20060905
PL  - Switzerland
TA  - Digestion
JT  - Digestion
JID - 0150472
RN  - 0 (8-sulfocholecystokinin octapeptide)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Receptors, Cholecystokinin)
RN  - M03GIQ7Z6P (Sincalide)
SB  - IM
MH  - Animals
MH  - Calcium Channels, L-Type/drug effects/metabolism
MH  - Female
MH  - Gastric Emptying/*physiology
MH  - Male
MH  - Muscle Contraction/*drug effects
MH  - Muscle, Smooth/drug effects/metabolism/*physiopathology
MH  - *Pyloric Antrum/drug effects/metabolism/physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cholecystokinin/*agonists
MH  - Signal Transduction/*drug effects
MH  - Sincalide/*analogs & derivatives/pharmacology
EDAT- 2006/09/07 09:00
MHDA- 2006/12/22 09:00
CRDT- 2006/09/07 09:00
PHST- 2006/02/13 00:00 [received]
PHST- 2006/09/07 09:00 [pubmed]
PHST- 2006/12/22 09:00 [medline]
PHST- 2006/09/07 09:00 [entrez]
AID - 95628 [pii]
AID - 10.1159/000095628 [doi]
PST - ppublish
SO  - Digestion. 2006;73(4):249-58. doi: 10.1159/000095628. Epub 2006 Sep 5.