PMID- 20205277 OWN - NLM STAT- MEDLINE DCOM- 20100520 LR - 20190430 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 16 IP - 9 DP - 2010 Mar 7 TI - Mechanisms mediating CCK-8S-induced contraction of proximal colon in guinea pigs. PG - 1076-85 AB - AIM: To investigate the effects of sulfated cholecystokinin octapeptide (CCK-8S) on the contractile activity of guinea-pig proximal colon. METHODS: Proximal colonic smooth muscle (PCSM) strips were obtained from adult female guinea pigs and contractile response of PCSM strips was recorded using a polyphysiograph. PCSM cells were isolated by enzymatic digestion. Resting potential (RP), action potential (AP), large conductance potassium channel currents (I(BKCa)) and L-type calcium currents (I(Ca-L)) were recorded by patch-clamp techniques. RESULTS: (1) CCK-8S (10(-7) mol/L) enhanced the mean contractile amplitude of colonic circular muscle and longitudinal muscle (LM) strips by 56.53% + or - 11.92% (P = 0.038) and 65.93% + or - 12.98% (P = 0.019), respectively, as well as the mean frequency of LM by 31.69% + or - 13.58% (P = 0.023), which were significantly attenuated by pretreating strips with devazepide, nifedipine, iberiotoxin, thapsigargin (TG) and BAPTA-AM (BA) respectively; (2) CCK-8S (10(-7) mol/L) increased the AP amplitude by 38.6% + or - 3.2% (P = 0.015), decreased AP duration by 36.9% + or - 8.7% (P = 0.026), and depolarized the RP from -61.3 + or - 2.7 mV to -29.8 + or - 5.9 mV (P = 0.032); and (3) Compared with the normal control group, CCK-8S (10(-7) mol/L) enhanced the peak current of I(BKCa) by 18.7% + or - 2.1% (from 916 + or - 183 pA to 1088 + or - 226 pA; at +60 mV; P = 0.029), which was inhibited by respective pretreatment with iberiotoxin and devazepide. Additionally, CCK-8S (10(-7) mol/L) intensified the peak current of I(Ca-L) by 40% (from 60 + or - 8 pA to 84 + or - 11 pA; at +10 mV; P = 0.012), compared to the normal control group, which was apparently suppressed by respective pretreatment with nifedipine, devazepide, TG and BA. In the respective presence of heparin and staurosporine, CCK-8S did not significantly enhance I(BKCa) and I(Ca-L). CONCLUSION: The results suggest that CCK-8S promotes guinea-pig proximal colon contraction by CCK1 receptors, following activation of the inositol triphosphate-protein kinase C signal transduction pathway. FAU - Zhu, Jie AU - Zhu J AD - Department of Gastroenterology, Renmin Hospital and Research Center of Structural Biology, Wuhan University, Wuhan 430060, Hubei Province, China. FAU - Chen, Ling AU - Chen L FAU - Xia, Hong AU - Xia H FAU - Luo, He-Sheng AU - Luo HS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (8-sulfocholecystokinin octapeptide) RN - 0 (Calcium Channels, L-Type) RN - 0 (Gastrointestinal Agents) RN - 0 (Large-Conductance Calcium-Activated Potassium Channels) RN - 0 (Membrane Transport Modulators) RN - 0 (Receptor, Cholecystokinin A) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 2.7.11.13 (Protein Kinase C) RN - M03GIQ7Z6P (Sincalide) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) SB - IM MH - Action Potentials MH - Animals MH - Calcium/metabolism MH - Calcium Channels, L-Type/drug effects/metabolism MH - Colon/*drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Gastrointestinal Agents/*pharmacology MH - Gastrointestinal Motility/*drug effects MH - Guinea Pigs MH - In Vitro Techniques MH - Inositol 1,4,5-Trisphosphate/metabolism MH - Large-Conductance Calcium-Activated Potassium Channels/drug effects/metabolism MH - Membrane Transport Modulators/pharmacology MH - Muscle Contraction/*drug effects MH - Muscle, Smooth/*drug effects/metabolism MH - Patch-Clamp Techniques MH - Potassium/metabolism MH - Protein Kinase C/metabolism MH - Receptor, Cholecystokinin A/drug effects/metabolism MH - Signal Transduction/drug effects MH - Sincalide/*analogs & derivatives/pharmacology MH - Time Factors PMC - PMC2835783 EDAT- 2010/03/06 06:00 MHDA- 2010/05/21 06:00 PMCR- 2010/03/07 CRDT- 2010/03/06 06:00 PHST- 2010/03/06 06:00 [entrez] PHST- 2010/03/06 06:00 [pubmed] PHST- 2010/05/21 06:00 [medline] PHST- 2010/03/07 00:00 [pmc-release] AID - 10.3748/wjg.v16.i9.1076 [doi] PST - ppublish SO - World J Gastroenterol. 2010 Mar 7;16(9):1076-85. doi: 10.3748/wjg.v16.i9.1076.