Effect Of Oxytocin On The Motility Of Colonic Smooth Muscle In Rabbits And The Mechanisms Involved

The functional dyspepsia and irritable bowel syndrome are related with the dysfunction of gastrointestinal motility. But medicine therapeutic in functional gastrointestinal disorders is still not effective. Investigating the nervous and humoral regulations of gastrointestinal motility and the mechanisms involved, will be of great importance for further manifesting the dysfunction of gastrointestinal motility involved or even finding new drugs for clinical use.Previous results have shown that oxytocin (OT) inhibits the gastric motility via vagal neurons of the dorsal motor nucleus, inhibits the gastric emptying and intestinal transit by increasing cholecystokinin secretion and excites phasic contraction of gallbladder via oxytocin receptor (OTR). However, the effects of OT on colonic motility have not been reported yet.OT exerts physiological actions via OTR in hypothalamus and uterus, which is regulated by estrodial and progesterone. Whether OT affects the colonic motility via OTR and whether its action is regulated by both estrodial and progesterone, need tobe further studied.The contraction of colonic smooth muscle can be caused via muscarinic receptor or motilin receptor. Whether the effects of OT on colonic smooth muscle are connected with M receptor and / or motilin receptor still need to be further studied.The present study was undertaken to investigate 1. the effects of OT on colonic smooth muscle; 2. the specific receptor involved and the action site of the effect of OT on colon; 3. the effect of female hormone on the action of OT; 4. the relationship between OT and M receptor and / or motilin receptor.Rabbits (Male or famale) were fasted overnight and sacrificed. The proximal colon and distal colon were removed. Four types of muscle strips parallel to either the circular or the longitudinal fibers were excised, which are named circular muscle of proximal colon (CP), longitudinal muscle of proximal colon (LP), circular muscle of distal colon (CD), and longitudinal muscle of distal colon (LD) respectively. The mucosa on each strip was carefully removed. Each of the 4 muscle strips was suspended in a tissue chamber containing 5 mL Krebs solution (37 °C) and bubbled continuously with 95 % O₂ and 5 % CO₂. One end of the strip was fixed at the bottom of the chamber. Another end was connected to an force transducer. Spontaneous contractile activities of colonic strips (under an initial tension of 1 g) were simultaneously recorded with an ink-writing recorder. The colonic strips were stabilized for 60 min. The effects of OT on colonic motility, the effects of specific antagonists such as OTR antagonist on OT - induced response, and the effect of OT on arecoline or erythromycin - induced responses were investigated. Statisticalcomparisons were performed by Sigmastat 2.0 software system. The results were expressed as x±s .P< 0.05 was considered as significant difference. The main results are shown as follows:1. OT decreased the mean contractile amplitude and the contractile frequency of LP, CP, LD and CD. The contractile activity of the distal colon decreased much more than that of proximal colon after OT administration.2. Vasopressin (VP) showed the biphasic action on CD, which decreased the mean contractile amplitude and contractile frequency and then increased resting tension 4 after VP administration. VP decreased the contractile frequency of LD, but not the mean contractile amplitude or the resting tension.3. Selective oxytocin receptor antagonist atosiban completely blocked the OT-induced decrease of contractile activity of both CD and LD. Krebs solution free of Mg2+ attenuated OT-induced response. Tetrodotoxin (an specific antagonist of sodium channel), N-co-nitro-L-arginine-methylester (an inhibitor of NO synthase), hexamethonium (an antagonist of N receptor), indomethacin (an inhibitor of PG synthesis) or verapamil (an antagonist of Ca2+ channel) did not block the OT-induced response.4. Both estradiol (E2) and progesterone (P) decreased the mean contractile amplitude, but not the contractile frequency of CD and LD. Both E2 and P enhanced the OT-induced decrease of the mean contractile amplitude and the contractile frequency of CD and LD.5. M receptor agonist arecoline (AR) dose-dependent increased the mean contractile...