Research On The Effect Of Cholecystokinin On Sensation Afferent Function Of Gastrointestinal Tract

Objective: The purpose of this study was to explore the effect ofcholecystokinin on sensation afferent function of gastrointestinal tract andthe corresponding mechanism. Methods: ⑴ Spontaneous and gastric distention - induced afferentdischarge of subdiaphragmatic vagus nerve was recorded in urethane -anesthetized rats. We investigated the effects of CCK and CCK-A receptorantagonist on the discharge of subdiaphragmatic vagus nerve as well as thecorresponding mechanism by intravenous injection of different dosage ofCCK (0.03, 0.06, 0.12 μg·kg-1) and loxiginmide (10 mg·kg-1). ⑵ Theeffects of gastric distention and intravenous CCK (0.06 μg·kg-1) onelectricity activity of gastric distention related neurons in the nucleus oftractus solitarius were investigated in urethane - anesthetized rats. In orderto know the mechanism corresponding, we also investigated the effects ofintravenous CCK (0.06 μg·kg-1) on the content of glutamic acid andgamma- aminobutyric acid in cerebrospinal fluid by high performanceliquid chromatography as well as intravenous injection of loxiginmide (10mg·kg-1) or section of cervical vagus nerve before intravenous injection ofCCK. Results: ⑴ Intravenous CCK caused obvious dose - dependentexciting effect on the spontaneous afferent discharge and inhibitory effecton the gastric distention induced afferent discharge of subdiaphragmaticvagus nerve. ⑵Loxiginmide, a CCK-A receptor antagonist, significantlyinhibited the effects of CCK mentioned above. The effects of intravenousCCK on both spontaneous discharge and gastric distention induceddischarge of subdiaphragmatic vagus nerve were inhibited when the ratswere pretreated with loxiginmide. ⑶Intravenous CCK can obviouslyinfluence the spontaneous activity of gastric distention related neurons inthe nucleus of tractus solitarius. Intravenous CCK can increase thedischarge of gastric distention (GD) excited neurons (9/14) and decreasethe discharge of GD inhibited neurons (5/14) in NTS. Howerer, the effectof CCK on gastric distention induced discharge of GD related neurons wasalways inhibitory. ⑷Intravenous CCK elicited changes in the content ofboth Glu and GABA in cerebrospinal fluid, the content of the two aminoacid increased obviously when pretreated with CCK. ⑸Pretreatment withloxiginmide or section of cervical vagus nerve before intravenous injctionof CCK, the effects of CCK on Glu and GABA content in CSF weresignificantly inhibited. Conclusion: ⑴ Circulating CCK elicits excitatory effect onspontaneous afferent discharge of subdiaphragmatic vagus nerve andinhibitory effect on gastric distention induced discharge of it. ⑵ Theaction of circulating CCK on afferent discharge of subdiaphragmaticvagus nerve is mediated by CCK-A receptor distributed in vagus nerve .⑶Circulating CCK and gastric distention have both excitatory andinhibitory effects on the electricity activity of gastric distention relatedneurons in NTS. But the effect of CCK on gastric distention induceddischarge of GD related neurons is inhibitory. The effect of gastricdistention on spantenous discharge of neurons in NTS is similar tocirculating CCK. ⑷ Glu and GABA in CSF may play an important rolein the effects of circulating CCK on the activity of GD related neurons inNTS. ⑸ The activation of peripheral CCK-A receptor and vagus nerve islikely to mediate the effects of CCK on the content of Glu and GABA inCSF.