CHOLECYSTOKININ STIMULATES NEURONAL RECEPTORS TO PRODUCE CONTRACTION OF THE CANINE COLON
CHOLECYSTOKININ STIMULATES NEURONAL RECEPTORS TO PRODUCE CONTRACTION OF THE CANINE COLON
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DOI：
10.1016/0024-3205(89)90615-2
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发表时间：
1989-01-01
期刊：
影响因子：
6.1
通讯作者：
ORMSBEE, HS
中科院分区：
文献类型：
--
作者：
BARONE, FC;BONDINELL, WE;ORMSBEE, HS
在戊巴比妥麻醉的狗中测定胆囊收缩素26-33-酰胺（CCK八肽；CCK-OP）和几种据称的CCK受体拮抗剂对犬结肠环肌的运动作用。静脉注射 CCK-OP 在收缩胆囊、胃和十二指肠的剂量下对结肠运动没有影响。通过动脉内注射将 CCK-OP 递送至近端结肠的一小段，产生与剂量相关的结肠运动增加，在 12 ng/kg 时出现一半最大反应，在 50 ng/kg 时出现最大反应。确定了动脉内注射几种已确定的 CCK 受体拮抗剂对近端结肠对动脉内注射 CCK-OP 的反应的影响。 Proglumide，10 mg/kg，本身不产生结肠收缩，但拮抗 CCK-OP 诱导的反应。苄氧基(CBZ)-CCK27-32-酰胺拮抗CCK-OP诱导的结肠反应并且对基础结肠运动也没有影响(0.1-1和5μg/kg)。这两种化合物都不会拮抗乙酰胆碱诱导的结肠反应。丁氧羰基 (BOC)-CCK31-33-酰胺可增加基础结肠运动，但在 0.1 和 0.2 mg/kg 剂量下不会改变 CCK-OP 诱导的反应。 0.1 mg/kg 剂量的二丁酰-cGMP 不影响基础运动或 CCK-OP 诱导的收缩。在 1.0 mg/kg 的剂量下，它增加了基础结肠运动，但不影响 CCK-OP 诱导的收缩。五胃泌素仅在5μg/kg的剂量下增加结肠运动活性，即比CCK-OP的有效剂量高得多的剂量。 CCK-OP 诱导的结肠运动效应的机制也已确定。硫酸阿托品，100μg/kg，静脉注射显着降低动脉内乙酰胆碱和 CCK-OP 诱导的最大结肠收缩。河鲀毒素在完全阻断神经元活动的静脉注射剂量下，不会影响最大乙酰胆碱诱导的收缩，但实际上消除了最大 CCK-OP 诱导的最大结肠反应。总之，动脉内 CCK-OP 产生犬近端结肠的环形肌肉收缩，这是通过刺激特定 CCK 受体介导的，CCK 受体产生胆碱能肠神经元释放乙酰胆碱。 Proglumide 和 CBZ-CCK27-32-amide 是这些结肠神经元受体的有效 CCK 受体拮抗剂。
The motor effects of cholecystokinin26-33-amide (CCK octapeptide; CCK-OP) and several purported CCK receptor antagonists on canine colonic circular muscle were determined in pentobarbital anesthetized dogs. Intravenous injections of CCK-OP had no effect on colonic motility at doses that contracted the gallbladder, stomach and duodenum. CCK-OP delivered by intraarterial injection to a small segment of the proximal colon produced a dose related increase in colonic motility with one-half maximum response at 12 ng/kg and maximum response at 50 ng/kg. The effects of intraarterial injections of several established CCK-receptor antagonists on proximal colonic responses to intraarterial injections of CCK-OP were determined. Proglumide, 10 mg/kg, did not produce colonic contractions itself, but antagonized CCK-OP-induced responses. Carbobenzyloxy (CBZ)-CCK27-32-amide antagonized CCK-OP-induced colonic responses and also had no effect on basal colonic motility (0.1-1 and 5 .mu.g/kg). Neither compound antagonized acetylcholine-induced colonic responses. Butoxycarbonyl (BOC)-CCK31-33-amide increased basal colonic motility, but did not alter CCK-OP-induced responses at doses of 0.1 and 0.2 mg/kg. Dibutyryl-cGMP at a dose of 0.1 mg/kg did not affect basal motility or CCK-OP-induced contractions. At a dose of 1.0 mg/kg it increased basal colonic motility but did not affect CCK-OP-induced contractions. Pentagastrin increased colonic motor activity only at a dose of 5 .mu.g/kg, i.a., a much higher dose than effective doses of CCK-OP. The mechanisms of CCK-OP-induced colonic motor effects also was determined. Atropine sulfate, 100 .mu.g/kg, i.v. significantly reduced both intraarterial acetylcholine- and CCK-OP-induced maximum colonic contractions. Tetrodotoxin, at intravenous doses that completely block neuronal activity, did not affect maximum acetylcholine-induced contractions but practically eliminated maximum CCK-OP-induced maximum colonic responses. In conclusion, intraarterial CCK-OP produces circular muscle contraction of the canine proximal colon that is mediated by stimulation of specific CCK receptors which produce the release of acetylcholine from cholinergic enteric neurons. Proglumide and CBZ-CCK27-32-amide are effective CCK receptor antagonists at these colonic neuronal receptors.