In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular Ca2+ ([Ca2+]i) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-HT2B, 3, 4, and 7 receptors in ICC. However, SDZ 205557 (a 5-HT4 receptor antagonist), SB 269970 (a 5-HT7 receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-HT3 antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-HT2B receptor antagonist). Based on [Ca2+]i analysis, we found that 5-HT increased the intensity of [Ca2+]i. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-HT3, 4, and 7 receptors via [Ca2+]i mobilization and regulation of mitogen-activated protein kinases.
Animals ; Flavonoids ; Gastrointestinal Motility ; Imidazoles ; Interstitial Cells of Cajal ; Intestine, Small ; Mice ; Mitogen-Activated Protein Kinases ; para-Aminobenzoates ; Patch-Clamp Techniques ; Phenols ; Pyridines ; Receptor, Serotonin, 5-HT2B ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT4 ; Serotonin ; Sulfonamides

BACKGROUNDOur previous studies have demonstrated that the levels of 5-hydroxytryptamine (5-HT) and 5-HT 2A receptor (5-HT2AR) in serum and platelet were associated with depression and myocardial infarction (MI), and pretreatment with ginseng fruit saponins (GFS) before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley (SD) rats with MI, depression, and MI + depression were evaluated.

METHODSA total of eighty SD rats were allocated to four groups: MI, depression, MI + depression, and control groups (n = 20 in each group). Each group included two subgroups (n = 10 in each subgroup): Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT2AR, and serotonin transporter (SERT) were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively.

RESULTSCompared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI + depression groups (serum: all P = 0.000; platelet lysate: P = 0.002, 0.000, 0.000, respectively). However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups (P = 0.025 and 0.044 respectively), and no significant difference was observed between saline and GFS treatment subgroups in MI + depression group (P = 0.663). Compared with that in GFS treatment subgroup of control group, the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI + depression groups (all P = 0.000). Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.009, 0.038, and P = 0.001, respectively), while the SERT levels of platelet lysate significantly decreased in GFS treatment subgroup of MI group (P = 0.000), significantly increased in GFS treatment subgroup of depression group (P = 0.019), and slightly changed in GFS treatment subgroup of MI + depression group (P = 0.219). No significant changes for SERT levels in brain homogenate could be found between the saline and GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.421, 0.076 and P = 0.642).

CONCLUSIONSThis study indicated that GFS might inhibit the reuptake of 5-HT from serum to platelet according to decreased 5-HT2AR in platelet and SERT in serum and platelet. The change of 5-HT in serum after GFS treatment was inconsistent with that in the brain. It seemed that GFS could not pass through the blood-brain barrier to affect the central serotonergic system.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Depression ; drug therapy ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Myocardial Infarction ; drug therapy ; Panax ; chemistry ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2B ; metabolism ; Saponins ; chemistry ; therapeutic use ; Serotonin ; metabolism ; Serotonin Plasma Membrane Transport Proteins ; metabolism