Oxytocin microinjected into dorsal motor nucleus of the vagus excites gallbladder motility via NMDA receptor-NO-cGMP pathway.
Our recent study indicated that, in the dorsal motor nucleus of the vagus (DMV), the N-methyl-D-aspartic acid (NMDA) receptor-nitric oxide (NO)-cGMP pathway participated in the regulation of gallbladder motility in rabbits. Oxytocin (OT) is involved as a neurotransmitter in autonomic regulation. The aim of the present experiments is to investigate the effect of OT microinjected into DMV on the gallbladder motility and the involvement of NMDA receptor-NO-cGMP pathway. A frog bladder connected with transducer was inserted into the gallbladder to record the gallbladder pressure. Microinjection of OT (10-50 nmol/L, 100 nl) dose dependently increased the strength of gallbladder phasic contraction. The excitatory effect of OT (10 nmol/L, 100 nl) was completely abolished by atosiban (10 mmol/L, 100 nl), the specific OT receptor antagonist, but was not influenced by [deamino-Pen(1), O-Me-Tyr(2),Arg(8)]-vasopressin (10 mmol/L, 100 nl), the V(1) receptor antagonist. Pretreatment of ketamine (10 mmol/L, 100 nl), the NMDA receptor antagonist, suppressed the gallbladder motor response to OT; but pretreatment of 6-Cyaon-7-Nitroquinoxaline-2,3-(1H,4H)-Dione (CNQX; 10 mmol/L, 100 nl), the non-NMDA receptor antagonist, did not affect it. Pretreatment of L-NAME (10 mmol/L, 100 nl), the nitric oxide synthase (NOS) inhibitor, or methyl blue (10 mmol/L, 100 nl), the guanylyl cyclase inhibitor, inhibited the excitatory effect of OT on gallbladder motility. Hence, we deduced that the microinjection of OT into the DMV enhanced the gallbladder motility through binding specific OT receptors and activating the NMDA receptor-NO-cGMP pathway.
Liu
Chuan Yong
CY
Institute of Physiology Medical School of Shandong University Jinan 250012 P. R. China. liucy@sdu.edu.cn
Xie
Dong Ping
DP
Liu
Ke Jing
KJ
Zhou
Yu Qin
YQ
Liu
Jing Zhang
JZ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000294:innervation; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012076:Renal Agents / Q000494:pharmacology; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
D001557:Benzenesulfonates; D016194:Receptors, N-Methyl-D-Aspartate; D012076:Renal Agents; C047046:atosiban; D009569:Nitric Oxide; D010121:Oxytocin; D007649:Ketamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C414357:Methyl Blue; D003894:Deamino Arginine Vasopressin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D014668:Vasotocin