八肽胆囊收缩素对大鼠大脑皮质细胞钙调素活性的影响

为了探讨胆囊收缩素(CCK)受体在中枢神经系统中的信号传递机制,观察了CCK₈和CCK_A受体拮抗剂L-364,718、CCK_B受体拮抗剂L-365,260对大鼠大脑皮质钙调素（CaM）活性的影响.结果表明：a.CCK₈对CaM活性的影响具有时间依赖性,15 min达到最高点后逐渐下降;b.CCK₈在10^－12～10^－7 mol/L范围内可刺激CaM活性的增加,超过10^－7 mol/L后,逐渐趋于饱和.c.CCK_A受体拮抗剂L-364,718、CCK_B受体拮抗剂L-365,260均可抑制10^－7 mol/L CCK₈引起的CaM活性的增加,但两者IC₅₀相差40倍,L-365,260在较低浓度时即能明显拮抗CCK₈引起的CaM活性变化.研究结果提示CCK₈可能通过CCK_B受体引起CaM活性变化,而CaM可能是CCK_B受体的重要信号传递机制之一.     

缩胆囊素受体拮抗剂对血浆缩胆囊素生物测定的影响

利用生物法测定了102例正常人空腹及进食二个油煎鸡蛋30min后血浆CCK浓度,结果分别为1.4±0.1pmol/L和4.9±0.4pmol/L(X±SE)。血浆CCK浓度不随性别和年龄而变化。本文研究了三种不同类型的CCK受体拮抗剂对CCK生物测定的影响。一组将L364,718(5.0nmol/L),丙谷胺(1.0mmol/L)或Bt_2-cGMP(0.1mmol/L)分别加入含8pmol/LCCK-8的人血浆,用SEP-PAK提取,另一组先提取血浆,于测定前向血浆提取物内加入上述拮抗剂,两组同时测定。结果显示,在有L364,718存在时仍可利用生物法测定血浆CCK浓度,如血中含有丙谷胺或Bt_2-cGMP则无法准确测定。     

创伤后抑制性T细胞对活化T细胞内白介素2及白介素2受体α基因表达的影响

研究了创伤小鼠抑制性T细胞(Ts)对白介素2(IL-2)及IL-2受体(IL-2R)α基因表达的抑制作用。结果表明,创伤后Ts细胞对正常活化T细胞内IL-2 mRNA及IL-2 RαmRNA水平的抑制作用增强,以伤后4天最为明显,伤后10天仍未恢复正常。创伤后Ts细胞还可升高正常活化T细胞内cAMP含量,降低cGMP含量,增加cAMP/cGMP比值。且可降低三磷酸肌醇(IP_3)含量、游离钙(Ca~(2 ))浓度、钙调素(CaM)、钙调素依赖性蛋白激酶(CaM-PK)及蛋白激酶C(PKC)的活性。去除创伤小鼠活化T细胞中的Ts细胞,则可使其IL-2mRNA及IL-2RαmRNA水平明显升高。并可使cAMP、cGMP、IP_3含量、Ca~(2 )浓度、CaM、CaM-PK及PKC活性的变化发生逆转。表明创伤后Ts细胞可通过影响T细胞内环核苷酸含量及磷脂酰肌醇代谢途径,进而抑制IL-2及IL-2 Rα的基因表达。     

甲胎蛋白受体的性质及其所介导的cAMP-PKA信号转导途径

研究HeLa细胞膜上甲胎蛋白 (alpha fetoprotein ,AFP)受体的存在情况及其介导的信号转导 .先用Na[12 5I]标记AFP ;标记的AFP和培养的HeLa细胞结合 ,Scatchard法和受体 配体结合法分析受体数目 ;再用放射免疫结合法分析在百日咳毒素 (pertussistoxin ,PTX)预处理前后AFP对细胞内环腺苷酸 (cAMP)浓度及细胞内蛋白激酶A(proteinkinaseA ,PKA)活性变化的影响 .在HeLa细胞膜表面存在 2种不同解离平衡常数 (Kd)的AFP受体 ,Kd1=5 2pmol L(2 10 0位点 细胞 ) ;Kd2 =2 3nmol L (114 0 0位点 细胞 ) .在AFP(2 0mg L)作用下 ,HeLa细胞内cAMP浓度变化及PKA活性的改变为与对照组比较 ,用PTX预处理前cAMP浓度升高 2 6 7% ,PKA活性增高 10 3 2 % ;用PTX预处理后升高 86 % ,PKA活性增高 2 5 3% .抗甲胎蛋白单克隆抗体可阻断AFP对细胞cAMP浓度和PKA活性的影响 .结果证明 ,在HeLa细胞膜上有 2种不同解离平衡常数的甲胎蛋白受体存在 ,受体有可能通过cAMP PKA途径介导信号转导 .     

aFGF对人脐静脉内皮细胞TPK、PKC活性及Ca~(2+)浓度的影响

为了观察酸性成纤维细胞生长因子 ( acidic fibroblast growth factor,a FGF)与人脐静脉内皮细胞 ( human umbilical vein endothelial cell,HUVEC)膜上特异受体结合后引起的细胞内信号转导途径 ,探讨 a FGF导致细胞增殖的机理 ,经 Scatchard曲线分析人脐静脉内皮细胞膜受体性质 .以不同浓度的 a FGF处理人脐静脉内皮细胞 ,利用 [γ- 3 2 P]ATP参入外源性底物的方法测定受体的酪氨酸蛋白激酶 ( tyrosine protein kinase,TPK)及蛋白激酶 C( protein kinase C,PKC)的活性 ;用 Fura-2 /AM为荧光指示剂测定 [Ca2 + ]i.结果显示 :Scatchard曲线证明 a FGF与 HUVEC膜受体特异结合呈一条曲线 ,即受体为一种结合位点 ,Kd 为 3.6× 1 0 -10～ 9.6× 1 0 -10 mol/L,每个细胞受体数为2 70 90 .随着 a FGF浓度增加 ,TPK及 PKC活性随之升高 .当 a FGF浓度为 1 .1 2 mg/L时 ,a FGF处理组的 TPK活性是对照组的 3倍 ;膜 PKC活性是对照组 3.4倍 ,胞浆 PKC活性是对照组的 1 .87倍 .胞浆 [Ca2 + ]是对照组的 3倍 .结果指出 :该细胞中 a FGF受体具有 TPK活性 .TPK激活后进一步促进蛋白质和酶磷酸化级联反应 ,而使 PKC活性及 [Ca2 + ]i 升高 ,即 PKC和 Ca2 + 为 TPK的下游信号分子 ,进一步促进基因表达增加 ,导致细胞增殖 .     

aFGF对人脐静脉内皮细胞TPK、PKC活性及Ca2+浓度的影响

为了观察酸性成纤维细胞生长因子 ( acidic fibroblast growth factor,a FGF)与人脐静脉内皮细胞 ( human umbilical vein endothelial cell,HUVEC)膜上特异受体结合后引起的细胞内信号转导途径 ,探讨 a FGF导致细胞增殖的机理 ,经 Scatchard曲线分析人脐静脉内皮细胞膜受体性质 .以不同浓度的 a FGF处理人脐静脉内皮细胞 ,利用 [γ- 3 2 P]ATP参入外源性底物的方法测定受体的酪氨酸蛋白激酶 ( tyrosine protein kinase,TPK)及蛋白激酶 C( protein kinase C,PKC)的活性 ;用 Fura-2 /AM为荧光指示剂测定 [Ca2 ]i.结果显示 :Scatchard曲线证明 a FGF与 HUVEC膜受体特异结合呈一条曲线 ,即受体为一种结合位点 ,Kd 为 3.6× 1 0 -10～ 9.6× 1 0 -10 mol/L,每个细胞受体数为2 70 90 .随着 a FGF浓度增加 ,TPK及 PKC活性随之升高 .当 a FGF浓度为 1 .1 2 mg/L时 ,a FGF处理组的 TPK活性是对照组的 3倍 ;膜 PKC活性是对照组 3.4倍 ,胞浆 PKC活性是对照组的 1 .87倍 .胞浆 [Ca2 ]是对照组的 3倍 .结果指出 :该细胞中 a FGF受体具有 TPK活性 .TPK激活后进一步促进蛋白质和酶磷酸化级联反应 ,而使 PKC活性及 [Ca2 ]i 升高 ,即 PKC和 Ca2 为 TPK的下游信号分子 ,进一步促进基因表达增加 ,导致细胞增殖 .     

甲硫氨酸脑啡肽和抗δ阿片受体抗体对小鼠骨髓瘤细胞信号传递系统的作用

为了探讨阿片肽与细胞表面受体结合后所产生的生物效应及其机制 ,用不同浓度甲硫氨酸脑啡肽 ( MENK)及抗 δ阿片受体单克隆抗体处理小鼠的骨髓瘤细胞 ( NS- 1 ) ,然后测定蛋白激酶A( PKA) ,蛋白激酶 C( PKC)活性及三磷酸肌醇 ( IP3 )含量 .研究结果表明 ,NENK可升高细胞胞浆及胞膜 PKA的活性 ,且这一作用可被抗δ阿片受体抗体所拮抗 .MENK对 PKC影响呈双向反应 ,0 .1 μmol/L MENK可以升高胞浆 PKC活性 ,但却明显降低胞膜 PKC活性 ;在 MENK浓度为 1 0μmol/L时则情况刚好相反 .1 μmol/L的 MENK可明显降低胞浆及胞膜 PKC活性 ,抗体可拮抗这种下调作用 .MENK可降低细胞内 IP3 的含量 ,且这一作用可被抗δ阿片受体抗体所拮抗 .由此可以推论 :MENK在与 δ阿片受体结合后 ,可以经过多种信号传导系统来调节细胞功能 ,从而产生不同的生物效应 .     

ACh对人垂体腺瘤细胞内蛋白激酶C、胞内游离钙及cAMP/cGMP的影响

我们曾发现ACh可明显地抑制垂体腺瘤细胞的增殖代谢,为深入探讨ACh抑制垂体腺瘤细胞增殖作用的机制,观察了ACh作用后垂体腺瘤细胞内蛋白激酶C(PKC)、[Ca^2 ]i及cAMP／cGMP的变化。结果发现：(1)与空白处理组相比,使用PKC的激动剂PMA处理培养的人垂体腺瘤细胞时可使胞浆、胞膜和细胞总PKC活性浓度均升高,但ACh(10μmol/L)作用15min后,胞浆、胞膜和细胞总PKC活性均下降,且此作用可被阿托品阻断;(2)ACh(10μmol/L)作用于单个人垂体腺瘤细胞后,立即使垂体腺瘤细胞[Ca^2 ]i相对水平降低,但此作用可被阿托品阻断;(3)ACh作用于人垂体腺瘤细胞15min后,胞内cAMP水平均明显升高,而cGMP没有改变。该结果为探讨ACh抑制垂体腺瘤细胞增殖的分子机制提供了重要线索,同时提示,ACh对垂体瘤细胞增殖分化的调控作用是细胞内多信息系统相互整合的结果。     

血管活性肠肽对肺表面活性物质结合蛋白A表达的影响

目的:研究血管活性肠肽(VIP)对肺表面活性物质结合蛋白A(SP-A)表达的影响以及VIP调控SP-A表达的细胞内信号转导途径.方法:运用免疫组织化学和RT-PCR技术研究VIP对SP-A表达的影响;并进一步运用受体拮抗、蛋白激酶抑制、反义寡核苷酸阻断等手段探讨VIP促进SP-A表达的信号转导途径.结果:①VIP(10-8mol/L)促进肺泡Ⅱ型细胞(ATⅡ)细胞中的SP-A蛋白表达和提高肺组织SP-AmRNA含量:②VIP受体拮抗剂(10-6mol/L)可取消VIP(10-8mol/L)促进SP-A表达的效应;③蛋白激酶C抑制剂H7(10-5mol/L)和c-fos基因的反义寡核苷酸(9×10 6mol/L)均可阻断VIP促进SP-A表达的作用.结论:VIP通过其受体促进SP-A的表达,PKC及c-fos蛋白在介导VIP促进SP-A表达的细胞内信号转导过程中起重要作用.     

普罗托品对大鼠胸主动脉血管平滑肌细胞内游离钙浓度和蛋白激酶C活性的影响

本实验室先前的研究已证实,普罗托品(protopine,Pro)舒张家兔主动脉的作用,可能与其增加血管平滑肌细胞内cAMP和cGMP水平有关.为了深入探讨Pro的扩血管作用机制,实验采用等张收缩记录大鼠离体血管条张力,利用Fura-2/AM负载的大鼠胸主动脉培养细胞直接测定细胞内游离Ca2+浓度([Ca2+]i),并应用同位素γ-32p-ATP催化活性法测定蛋白激酶C(PKC)活性等方法,分别观察了Pro的相关效应.结果表明,Pro(30和100 μmol/L)明显降低去甲肾上腺素(NA)和高钾所致的动脉条收缩幅度,使二者的量效曲线呈非平行右移,最大反应压低;pD2'值分别为3.7±0.25和3.97±0.15;Pro(50和100μmol/L)对静息状态下[Ca2+]i没有任何影响,但对NA和高钾引起的[Ca2+]i升高均有明显抑制作用;Pro(30和100 μmol/L)对未经NA处理血管条的胞浆和胞膜PKC活性均无明显影响;但在NA预处理的血管条,Pro使NA所升高的胞浆内PKC的活性趋于降低,而明显升高胞膜PKC的活性,对PKC的总活性无明显影响.结果提示,在有NA存在的情况下,Pro似能促使PKC从胞浆向细胞膜转移,其扩血管效应似为其降Ca2+作用、升高cAMP和cGMP的作用及其对PKC影响等几方面的综合结果.     

Brain CCKA receptors mediate the colonic motor response to feeding in dogs

The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10 micrograms/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCKA receptors.     

Cholecystokinin Modulates the Release of Dopamine from the Anterior and Posterior Nucleus Accumbens by Two Different Mechanisms

The effects of various cholecystokinin (CCK)-related peptides were investigated on 35 mM K(+)-stimulated endogenous dopamine release from slices of either anterior or posterior nucleus accumbens of the rat. CCK sulphated octapeptide (1-10 microM), but not pentagastrin or CCK unsulphated octapeptide, was found to cause a dose-dependent increase in the release from the posterior nucleus accumbens. This effect was blocked by low doses of the CCKA receptor antagonist L364,718 (10 nM) but not the CCKB receptor antagonist L365,260. In the anterior nucleus accumbens CCK sulphated octapeptide (1 microM) and CCK unsulphated octapeptide (0.1-1 microM) inhibited the dopamine release, and this effect was blocked by L365,260 (10-100 nM) but not by L364,718. These results suggest that CCK has a different effect on dopamine release from the anterior and posterior nucleus accumbens and that these effects are mediated by two different types of CCK receptor.     

Effects of selective cholecystokinin antagonists L364,718 and L365,260 on food intake in rats

The selective type A and B cholecystokinin (CCK) receptor antagonists L364,718 and L365,260 were used to identify the receptor subtype that mediates the satiety effect of endogenous CCK. Male rats (n = 12–13/group), fed ground rat chow ad lib, received L364,718 (0, 1, 10, 100, or 1000 μg/kg IP) or L365,260 (0, 0.1, 1, 10, 100, 1000, or 10,000 μg/kg IP) 2 h after lights off, and food intake was measured 1.5, 3.5, and 5.5 h later. L364,718 significantly stimulated 1.5-h food intake by more than 40% at 10 μg/kg and higher doses; cumulative intake at 3.5 and 5.5 h remained elevated by about 20% at 1000 and 100 μg/kg of L364,718, respectively. In contrast, L365,260 had no significant stimulatory effect on feeding at any dose. The potency of L365,260 for antagonizing gastrin-stimulated gastric acid secretion was examined in unanesthetized rats. Male rats (n = 14), prepared with gastric and jugular vein cannulas, received doubling doses of gastrin (G-17I) (0.16–5 nmol/kg/h IV), each dose for 30 min, and gastric juice was collected for each 30-min period. G-17I stimulated gastric acid output dose dependently; the minimal effective dose was 0.16 nmol/kg/h, while maximal output (5-fold above basal) occurred at 5 nmol/kg/h. L365,260 (0, 1, 10, 100, 1000, or 10,000 μg/kg IV), administered 30 min before continuous infusion of G-17I (1.25 or 5 nmol/kg/h), significantly inhibited acid output only at 10,000 μg/kg; cumulative 60-min output was decreased by 60%. These results suggest that CCK acts at CCK-A receptors to produce satiety during the dark period in ad lib-feeding rats.     

Inhibition of cell proliferation by the cholecystokinin antagonist L-364,718

Specific cholecystokinin (CCK) receptor and gastrin receptor antagonists were used to assess what role, if any, these receptors have in autocrine cell growth. Although the cholecystokinin receptor antagonist, L-364,718, inhibited cell proliferation in a broad spectrum of cell lines, the gastrin antagonist, L-365,260, had no effect on cell proliferation. In addition neither added gastrin17, nor sulfated cholecystokinin8, could reverse the inhibitory action of L-364,718. It is proposed that L-364,718 inhibits cell proliferation independently of classical gastrin/CCK receptors.     

Biological effects of newly synthesized cholecystokinin analogs

Cholecystokinin (CCK) is a gut hormone that regulates pancreatic endocrine functions via CCK(A) receptors. CCK(4) (Trp-Met-Asp-Phe-NH(2)) has an insulinotropic effect, but is 1,000-fold less potent than CCK(8) in rodents. The in vitro potencies with respect to binding, the biological effects and the selectivity of newly synthesized CCK(4) analogs constructed by computer modelling experiments were investigated in vitro in rat pancreas and brain, INS-1 cells, and guinea pig ileum. Exchanging various amino acids, e.g. Met by either Pro or Nle, and modifying Phe by adding various substituents in different positions led to compounds which were more effective as insulin secretagogues than CCK(4) itself and even show insulinotropic effects comparable with those of CCK(8) (e. g. compounds M1 and M2 being substituted at Phe). Some compounds which possess electron withdrawing groups on the C-terminal Phe and possess a Pro instead of a Met were especially effective. The CCK(A) receptor antagonist L-364,718, but not by the CCK(B) receptor antagonist L-365,260, inhibited the insulinotropic effects. The synthetic CCK(4) compounds were not selective for the endocrine pancreas: e.g. M1 and M2 had binding activity with respect to rat brain homogenates but no activity with respect to contraction of the guinea pig ileum. The data indicate that some of the newly synthesized CCK tetrapeptides exhibit a high affinity for the CCK receptor of beta-cells and have an insulinotropic effect much higher than CCK(4).     

Increased circulating cholecystokinin contributes to anorexia and anxiety behavior in mice overexpressing pancreatic polypeptide

We have previously reported that pancreatic polypeptide (PP) overexpressing mice display thin phenotype with delayed gastric emptying and decreased food intake. In the present study, we further examined if CCK contributes to anorexia and anxiety behavior in PP overexpressing mice. Plasma CCK levels in PP overexpressing mice and their littermates were determined by radioimmunoassay using antisera specific to sulfated CCK-8 and CCK-33. To elucidate the role of CCK in PP overexpressing mice, CCK-1 receptor antagonist (L-364,718) or saline was administered intraperitoneally and food intake was measured for 2 h. CCK-2 antagonist (L-365,260) or saline was injected intraperitoneally and the elevated plus-maze test was performed to assess anxiety. Plasma CCK levels were significantly increased in PP overexpressing mice. Administration of L-364,718 increased food intake in PP overexpressing mice compared to the saline-injected PP overexpressing group, while L-364,718 did not increase food intake in non-transgenic littermates. PP overexpressing mice exhibited anxiety in the plus-maze test. Administration of CCK-2 receptor antagonist (L-365,260) reversed the decreased percentage of entry into the open arms in PP overexpressing mice. These results indicated that elevated CCK may contribute to anorexic and anxious phenotype of PP overexpressing mice.     

CCK antagonists interact with CCK-B receptors on human small cell lung cancer cells

The ability of cholecystokinin (CCK) receptor antagonists to interact with CCK receptors in small cell lung cancer (SCLC) cells was investigated. L-365,260, CCK-8, L-364,718, CBZ-CCK(27-32)-NH2 and proglumide analogue 10 inhibited specific 125I-CCK-8 binding to SCLC cells with IC50 values of 0.2, 2, 500, 100,000 and 500,000 nM, respectively. Gastrin-I and CCK-8 elevated the cytosolic Ca2+ when SCLC cells were loaded with Fura 2-AM. L-365,260 inhibited the cytosolic Ca2+ increase caused by 10 nM CCK-8 in a dose-dependent manner. The effects of 10 nM L-365,260 were reversed by high concentrations of CCK-8. These data indicate that L-365,260 functions as a reversible CCK-8 antagonist using SCLC cells.     

Effects of Cholecystokinin Peptides and GV 150013, a Selective CholecystokininB Receptor Antagonist, on Electrically Evoked Endogenous GABA Release from Rat Cortical Slices

The effects of cholecystokinin (CCK) agonists and antagonists on spontaneous and electrically evoked endogenous GABA release from rat cerebral cortex slices were evaluated. Neither the nonselective and CCK(B)-selective receptor agonists CCK-8S (3-1,000 nM) and CCK-4 (3-1,000 nM), respectively, nor the selective CCK(B) and CCK(A) receptor antagonists GV 150013 (3-30 nM) and L-364,718 (10-100 nM), respectively, significantly affected spontaneous GABA release. CCK-8S (1-1,000 nM) and CCK-4 (1-1,000 nM) increased the electrically (5 and 10 Hz)-evoked GABA release. On the contrary, GV 150013 (10 and 30 nM) significantly decreased the electrically evoked GABA release only when the slices were stimulated at the higher 10 Hz frequency. The CCK-8S- and CCK-4-induced increases in electrically evoked GABA release were counteracted by GV 150013, but not by L-364,718. Furthermore, GV 150013 at 3 nM shifted to the right the CCK-4 concentration-response curve, whereas at the higher 10 nM concentration it dramatically flattened the curve. Finally, in cortical slices obtained from rats chronically treated with GV 150013, the concentration-response curve of CCK-4 was shifted to the left and the peak effect of the peptide was significantly higher than that observed in naive animals. These results suggest that CCK increases electrically evoked, but not spontaneous, endogenous GABA release from rat cortical slices, possibly by activating local CCK(B) receptors. In addition, chronic treatment with the novel CCK(B) receptor antagonist GV 150013 leads to an enhanced responsiveness of cortical slices to CCK-4 application.     

The effects of antagonists of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365,260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.     

Effects of CCK antagonists on CCK-induced suppression of locomotor activity in mice.

Sulfated cholecystokinin octapeptide (CCK-8) was administered either intraperitoneally or into the cerebral ventricle of fully conscious mice, and locomotor activity was quantified. CCK-8 administered by either route suppressed locomotor activity. Subcutaneously administered selective CCK-A receptor antagonist, L-364,718 (1 mg/kg), reversed the inhibitory effect of centrally as well as peripherally administered CCK-8, but the selective CCK-B receptor antagonist, L-365,260 (1 mg/kg), did not. These results demonstrate that centrally as well as peripherally administered CCK-8 suppresses locomotor activity in mice through an interaction with CCK-A, but not CCK-B, receptors.