Mechanisms mediating CCK-8S-induced contraction of proximal colon in guinea pigs
2010
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 (IBKCa) and L-type calcium currents (ICa-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% ± 11.92% (P = 0.038) and 65.93% ± 12.98% (P = 0.019), respectively, as well as the mean frequency of LM by 31.69% ± 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% ± 3.2% (P = 0.015), decreased AP duration by 36.9% ± 8.7% (P = 0.026), and depolarized the RP from -61.3 ± 2.7 mV to -29.8 ± 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 IBKCa by 18.7% ± 2.1% (from 916 ± 183 pA to 1088 ± 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 ICa-L by 40% (from 60 ± 8 pA to 84 ± 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 IBKCa and ICa-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.
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