Xinmin Si

Publications (2)4.16 Total impact

• Article: Role of calcium in activation of hyperpolarization-activated cyclic nucleotide-gated channels caused by cholecystokinin octapeptide in interstitial cells of cajal.

  Xinmin Si, Lei Huang, Yaoyao Gong, Jia Lu, Lin Lin
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  ABSTRACT: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate pacemaker activity in some cardiac cells and neurons. Little is known about the effects of cholecystokinin octapeptide (CCK-8) on HCN channels and excitability of murine interstitial cells of Cajal (ICCs). In the present study, the effects and mechanisms of CCK-8 on HCN channels were investigated by measuring mechanical contraction of smooth muscle strips and ionic channels of ICCs in murine gastric antrum. Sulfated CCK-8 (CCK-8S) was used, and we found that CCK-8S increased the contraction of smooth muscle strips in the gastric antrum, which could be suppressed by specific HCN channel blockers CsCl and ZD7288. Extracellular calcium could also intensify the contraction. Under the same conditions, when antral strips were exposed to calcium ion (Ca²⁺)-free solution, no significant changes could be recorded with CCK-8S or ZD7288. Isolated ICCs from the murine gastric antrum identified by specific c-Kit antibody primers were chosen for electrophysiological recordings. HCN current (I(h)) of cultured ICCs was studied by whole-cell patch clamp techniques. A spontaneous transient inward current was recorded in ICCs, which could be inhibited by addition of CsCl and ZD7288; the current proved to be I(h). CCK-8S-facilitated I(h) in cultured ICCs could be inhibited by CsCl and ZD7288. When cultured ICCs were exposed to Ca²⁺-free solution, no significant changes could be recorded by application of CCK-8S on I(h), which proved extracellular calcium might have an excitatory effect on HCN channels. We demonstrate that HCN channels are present in ICCs in the murine gastric antrum; they might be an important regulator of ICC excitability and pacemaker activity and are strongly affected by CCK-8S. Extracellular calcium might be a trigger in the activation of HCN channels caused by CCK-8S in cultured ICCs.
  Digestion 04/2012; 85(4):266-75. · 2.05 Impact Factor
• Article: Inhibitory effects of somatostatin on cholecystokinin octapeptide induced bile regurgitation under stress: ionic and molecular mechanisms.

  Xinmin Si, Lei Huang, Hesheng Luo, Ruihua Shi
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  ABSTRACT: To investigate the possible effects and related ionic and molecular mechanisms of changes of plasma cholecystokinin octapeptide and somatostatin on stress-induced bile regurgitation in rats. In forty healthy adult rats, changes of plasma cholecystokinin octapeptide, somatostatin and intragastric bile concentration under stressful condition were respectively measured by specific radioimmunoassay methods. Contractile responses of gastric antral smooth strips isolated from healthy adult rats were recorded by polyphysiograph. Immunoprecipitation was used to determine the regulatory effect of protein kinase C on regulating the phosphorylation of type 3 inositol 1,4,5-triphosphate receptor (InsP3R3) in gastric smooth muscle cells. Changes of intracellular calcium fluorescence intensity of smooth muscle cells presented as intracellular calcium ([Ca2+]i) were analyzed under laser scanning confocal microscopy and L-type voltage-dependent calcium currents of smooth muscle cells were recorded by patch-clamp techniques. Compared with the normal control group, plasma cholecystokinin octapeptide and gastric bile concentration of each stress group significantly increased during the stress, while adverse effect was obtained in plasma somatostatin, which decreased from the beginning of the stress and attained the minimum nearly at the same time when the plasma cholecystokinin octapeptide concentration reached the maximum. Respective addition of cholecystokinin octapeptide and somatostatin with increasing concentrations caused rapid, sustained, concentration-dependent increase and decrease in muscle contraction of gastric antral strips, and cholecystokinin octapeptide that increased the contractile response could be blocked by respective administration of nifedipine and somatostatin significantly. Similar results were obtained in the changes of calcium fluorescence intensity and calcium currents of smooth muscle cells. Pretreatment with somatostatin significantly increased cholecystokinin octapeptide-increased phosphorylation of InsP3R3 in smooth muscle cells. Gastric mucosal damage induced by bile regurgitation is closely connected with gastric antral dysmotility evoked by the changes of cholecystokinin octapeptide and somatostatin under stressful condition. Cholecystokinin octapeptide-intensified contraction depends on the release of intracellular calcium stores and the influx of extracellular calcium via L-type voltage-dependent calcium channels, while this excitatory effect of cholecystokinin octapeptide could be blocked by somatostatin, suggesting that both of the two peptides play important roles in the regulation of gastric motility.
  Regulatory Peptides 06/2009; 156(1-3):34-41. · 2.11 Impact Factor