支气管哮喘大鼠肺内非肾上腺素能非胆碱能神经分布及神经肽含量的相关性研究

目的探讨支气管哮喘（简称哮喘）大鼠肺内非肾上腺素能非胆碱能（non—adrenergicnon—cholinergic,NANC）神经分布及其神经肽含量的变化并分析两者的相关性。方法20只Wister大鼠随机分成正常组和哮喘组。采用免疫组织化学和计算机图象分析观察大鼠肺内降钙素基因相关肽（calcitoningene-relatedpeptide,CGRP）和血管活性肠肽（vasoactiveintestinalpeptide,VIP）免疫反应阳性纤维的变化,并且用酶联免疫吸附试验法测定肺泡灌洗液中CGRP和VIP的浓度。结果①哮喘大鼠肺内CGRP和VIP阳性纤维的分布和密度均发生了显著的变化,CGRP阳性纤维显著增多,染色加深,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义（P〈0．01）;VIP阳性纤维明显缺乏,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义（P〈0．05或P〈0．01）。②哮喘大鼠肺泡灌洗液中CGRP的浓度与正常对照组相比显著增高（P〈0．01）,与CGRP阳性纤维的相对染色面积（r=0．903）和光密度值（r=0．880）呈正相关;VIP的浓度显著降低（P〈0.01）,与VIP阳性纤维的相对染色面积（r=0．899）和光密度值（r=0．878）呈正相关。结论哮喘大鼠肺内NANC神经分布异常,这可能是导致相应的神经肽含量变化的直接原因。     

钙调神经磷酸酶在支气管哮喘大鼠气道重塑中的作用

目的 通过测定支气管哮喘(简称哮喘)大鼠肺组织中钙调神经磷酸酶(calcineurin,CaN)蛋白、Mrna的表达及CaN的活性,探讨CaN在哮喘大鼠气道重塑中的作用.方法 将20只Wistar大鼠随机分为哮喘组和对照组,每组10只.鸡卵清白蛋白溶液致敏及激发复制大鼠哮喘模型.HE染色观察气道炎症情况;图像分析观察支气管管壁厚度;实时定量(Real-time)PCR测定肺组织中CaN Mrna水平;免疫组织化学法检测肺组织中CaN蛋白的相对表达量;生物化学法检测大鼠肺组织CaN活性;流式细胞仪测定外周血单个核细胞细胞周期时相分布;ELISA法测定血浆中白介素4(IL-4)和肿瘤坏死因子α(TNF-α)的含量.结果 ①哮喘组大鼠支气管管壁厚度较对照组明显增加(P＜0.01);②哮喘组大鼠肺组织中CaNmRNA水平的相对表达量、CaN蛋白的相对表达量及CaN的活性均较对照组高(分别P＜0.05、P＜0.01和P＜0.01);③哮喘组大鼠血浆中IL-4和TNF-α含量较对照组明显增加(分别P＜0.01,P＜0.05);④与对照组相比,哮喘组大鼠外周血单个核细胞处于G0/G1期的百分率降低,处于S期、S+G2/M期百分率增加(P值均＜0.01);⑤大鼠肺组织CaN活性分别与大鼠支气管管壁厚度呈正相关(P＜0.01),与处于S期、S+G2/M期的外周血单个核细胞百分率呈正相关(P值均＜0.05),与血浆中IL-4的含量呈正相关(P＜0.05);血浆中IL-4含量与TNF-α含量及大鼠支气管管壁厚度亦呈正相关(P值均＜0.05).结论 哮喘大鼠肺组织CaN的活性增加,其可能通过促进外周血单个核细胞的分裂、增殖及活化产生IL-4和TNF-α而参与哮喘气道重塑的形成.     

血管活性物质在大鼠肝肺综合征发病机制中的作用

目的:探讨内皮素-1(endothelin-1,ET-1)、一氧化氮(nitric oxide,NO)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在大鼠肝肺综合征(hepatopulmonary syndrome,HPS) 发病机制中的作用.方法:健康Wistar大鼠32只随机平均分为假手术组、CBDL术后3 wk组、4 wk组、5 wk组.采用胆总管结扎(common bile duct ligation, CBDL)术制备大鼠HPS模型成功后,行肝功能及肝肺病理检查.放射免疫分析法检测大鼠血浆和肝组织、肺组织匀浆中ET-1和CGRP的水平,利用硝酸还原酶法检测大鼠血清和肝、肺组织匀浆中NO的水平.结果:在大鼠HPS形成过程中,肝细胞变性、坏死,大量纤维组织增生,形成假小叶.肺泡毛细血管增生、扩张.伴肺泡间隔增宽、容量减小.术后3-5 wk,CBDL组大鼠血浆和肝、肺组织匀浆中ET-1、NO、CGRP水平显著升高,且与ALT水平呈正相关(血浆,ET-1:r=0.9889,P=0.0111:NO:r-=0.9935,P=0.0065;CGRP:r=0.9714.P=0.0286;肝组织:r=0.9969,P=0.0035;r=0.9993,P=0.0070;r=0.9507,P=0.0493;肺组织:r=0.9939,P=0.0061;r=0.9991,P=0.0009;r=0.9557,P=0.0443).结论:在大鼠HPS形成过程中,血浆和肝、肺组织匀浆中ET-1,NO和CGRP水平持续升高,提示血管活性物质ET-1,NO和CGRP在其发病机制中可能起着一定作用.     

2型糖尿病大鼠肺组织内皮素-1、降钙素基因相关肽及P物质水平变化及其对肺动脉高压的影响

目的 探讨2型糖尿病大鼠肺组织内皮素-1(ET-1)、降钙素基因相关肽(CGRP)、P物质(SP)的变化.方法 3个月龄健康雄性Wistar大鼠10只,采用高脂饲料喂养联合30μg/g链脲佐菌素尾静脉注射制备2型糖尿病大鼠模型.另设正常对照组(n=8),给予普通饮食.造模成功后12周末股动脉放血处死大鼠,取右下肺组织行Weigert来复红弹力纤维染色,计算与呼吸性细支气管、肺泡管伴行的肺小动脉管壁厚度占血管外径百分比(WT%)以及管壁面积占血管总面积百分比(WA%).应用免疫组织化学方法观察肺组织ET-1、CGRP、SP表达水平.数据统计采用独立样本t检验.结果 与正常对照组比较,糖尿病组大鼠肺泡隔面积与视场总面积比(0.42±0.10 vs 0.29±0.06,t=5.842,P＜0.05)、肺动脉WT%(26%±8%vs 19%±9%,t=3.023,P＜0.05)和WA%(42%±8% vs 36%±9%,t=2.526,P＜0.05)均显著增加,ET-1、SP平均吸光度(ET-1:86±5 vs 83±4,t=2.402,P＜0.05;SP:101±4 vs 100±3,t=2.530,P＜0.05)和阳性面积/视场总面积比(ET-1:0.016±0.017 vs0.010±0.008,t=2.501,P＜0.05;SP:0.014±0.014 vs 0.009±0.009,t=2.127,P＜0.05)显著增加,CGRP平均吸光度和阳性面积/视场总面积比差异无统计学意义.结论 糖尿病大鼠存在肺动脉高压的病理结构改变,可能与其肺组织ET-1表达增加有关.     

肠易激综合征患者内脏高敏感性的机制研究

目的检测肠易激综合征(IBS)患者的内脏感觉及其结肠黏膜肥大细胞(MC)、P物质(SP)和血管活性肠肽(VIP)的改变,探讨MC、SP、VIP对IBS患者内脏高敏感性的作用及其机制.方法黏膜标本取自19例正常人和22例腹泻型IBS(D-IBS)、20例便秘型IBS(C-IBS)患者回肠末端、回盲部、升结肠、乙状结肠,应用特殊组织化学染色法、免疫组织化学染色法分别对MC、SP和VIP免疫反应阳性神经纤维进行染色,应用彩色病理图像分析软件进行分析,电镜观察MC及其毗邻结构;应用电子气压泵及灌注导管测压仪检测上述患者肛门直肠压力、直肠对容量刺激的感觉及直肠顺应性.结果IBS组回肠末端、回盲部、升结肠MC明显增多,MC显著变异(P＜0.01);IBS组结肠黏膜SP、VIP免疫反应阳性神经纤维较正常对照组增多、增粗、阳性强度增强(P＜0.01);IBS组SP、VIP免疫反应阳性纤维的阳性强度均值、面积与MC的密度、面积密切相关(r=0.3860～0.6632,P＜0.01、P＜0.05),并可观察到MC与无髓神经末梢及浆细胞等内分泌细胞毗邻或密切接触;IBS组肛门直肠括约肌的静息压、收缩压、松弛压与正常对照组相似(P＞0.05),感觉阈值、排便阈值、疼痛阈值明显低于正常对照组(P＜0.01),直肠顺应性降低(P＜0.01),向直肠内注气20或40 ml后均可引起直肠肛门抑制性反射.结论MC、SP、VIP在IBS的病理生理机制中可能起关键性作用,MC活性、SP、VIP免疫反应阳性神经纤维可能与IBS以内脏感觉及动力变化为特征的内脏高敏感性相关联.     

PTEN在支气管哮喘大鼠气道炎症中的作用

目的 探讨PTEN在支气管哮喘(简称哮喘)大鼠气道炎症中的作用.方法 20只SPF级雄性SD大鼠随机分为2组,对照组和哮喘组.以卵清白蛋白致敏激发法复制大鼠哮喘模型,每只大鼠左肺留取肺组织,右肺进行支气管肺泡灌洗并留取支气管肺泡灌洗液(BALF).对BALF进行细胞分类计数;应用双抗体夹心酶联免疫吸附试验(Sandwich ELISA)法测定BALF中IL-4、IL-12浓度;采用免疫组织化学法和Western blot法测定PTEN蛋白的表达和量的变化.结果 ①BALF IL-4的浓度哮喘组显著高于对照组,BALF中IL-12的浓度哮喘组显著低于对照组(P值均＜0.01);②免疫组织化学显示PTEN蛋白主要表达细胞是支气管上皮细胞,Western blot法显示哮喘组支气管PTEN蛋白的表达显著低于对照组(P＜0.01);③支气管上皮细胞PTEN蛋白表达量分别与BALF中的IL-4浓度呈显著负相关,与BALF中的IL-12浓度呈显著正相关.结论 哮喘大鼠PTEN蛋白表达明显减少,它能减少Th2因子的表达,可能与哮喘大鼠气道炎症中Th1/Th2平衡密切相关.     

慢性阻塞性肺疾病大鼠模型中骨骼肌蛋白降解机制的研究

目的 研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠模型的骨骼肌蛋白降解机制,为有效防治COPD患者骨骼肌蛋白高分解,功能障碍等难题提供科学理论和依据.方法 成年雄性SD大鼠30只,分为模型组18只,对照组12只,采用反复熏香烟和气管内注入脂多糖复制COPD大鼠模型.酶联免疫吸附法(ELISA)测定血清和膈肌组织中的白介素6(IL-6),肿瘤坏死因子α(TNF-α),γ干扰素(IFN-γ)等含量.蛋白免疫印迹法测定大鼠膈肌和腓肠肌内的E2-14K、MAFbx、MuRF-1的蛋白表达.结果 在模型组中,血清和膈肌内的IL-6、TNF-α均较对照组显著升高,IFN-γ则较对照组显著降低.Western blot的结果显示:膈肌组织中E2-14K、MAFbx、MuRF-1均较对照组表达明显增强(各蛋白的相对表达量分别为0.96±0.12 vs 0.53±0.09、0.99±0.10 vs 0.53士0.08、0.95±0.08 vs 0.51±0.16,P＜0.0l).腓肠肌中E2-14K、MAFbx、MuRF-1亦较对照组表达增强(各蛋白的相对表达量分别为0.98±0.06 vs 0.83士0.05、1.00±0.04 vs 0.81±0.05、0.92±0.05 vs0.71±0.05,P＜0.05).体质量与TNF-α呈显著负相关(血清r=-0.84,膈肌r=-0.75,P值均＜0.01),与IFN-γ呈正相关(血清r=-0.71,膈肌r=-0.69,P值均＜0.01)；中性粒细胞百分比与1L-6呈正相关(血清r =0.82,膈肌r=0.91,P值均＜0.01)；膈肌组织中,IL-6、TNF-α的水平与膈肌的E2-14K、MAFbx、MuRF-1灰度值呈显著正相关,相关系数分别为r=0.86、r=0.94、r=0.89,P＜0.01和r=0.84、r=0.83、r=0.84,P＜0.01；IFN-y与E2-14K、MAFbx、MuRF-1灰度值呈显著负相关,相关系数为r =0.81、r=0.80、r=0.78,P＜0.01.结论 在COPD大鼠模型中,炎症因子、免疫调节因子的表达失衡和骨骼肌内泛素及泛素化蛋白的过度表达可能是引起骨骼肌蛋白降解加快的重要原因.     

支气管哮喘大鼠细胞周期蛋白D1与气道重塑关系的研究

目的 观察支气管哮喘(简称哮喘)大鼠模型肺组织中细胞周期蛋白D1的表达变化,以及细胞周期蛋白D1与气道重塑的关系.方法 16只SD大鼠随机分成正常组和哮喘组,每组8只.应用卵清蛋白致敏和激发的方法建立哮喘大鼠动物模型.HE染色观察气道炎症情况,采用马松染色观察气道胶原沉积变化,免疫组织化学和蛋白印迹法观察细胞周期蛋白D1的表达变化,免疫组织化学法观察气道平滑肌肌动蛋白-α表达变化.结果 哮喘组大鼠气道胶原沉积、细胞周期蛋白D1和肌动蛋白-α表达较正常组明显增高(P＜0.05),哮喘组肌动蛋白-α与细胞周期蛋白D1表达呈明显正相关(r1=0.20,P＜0.05;r2=0.53,P＜0.05).结论 细胞周期蛋白D1参与哮喘气道重塑的调节.     

支气管哮喘大鼠细胞周期蛋白D1与气道重塑关系的研究

目的 观察支气管哮喘(简称哮喘)大鼠模型肺组织中细胞周期蛋白D1的表达变化,以及细胞周期蛋白D1与气道重塑的关系.方法 16只SD大鼠随机分成正常组和哮喘组,每组8只.应用卵清蛋白致敏和激发的方法建立哮喘大鼠动物模型.HE染色观察气道炎症情况,采用马松染色观察气道胶原沉积变化,免疫组织化学和蛋白印迹法观察细胞周期蛋白D1的表达变化,免疫组织化学法观察气道平滑肌肌动蛋白-α表达变化.结果 哮喘组大鼠气道胶原沉积、细胞周期蛋白D1和肌动蛋白-α表达较正常组明显增高(P＜0.05),哮喘组肌动蛋白-α与细胞周期蛋白D1表达呈明显正相关(r1=0.20,P＜0.05; r2=0.53,P＜0.05).结论 细胞周期蛋白D1参与哮喘气道重塑的调节.     

幽门螺杆菌感染慢性阻塞性肺病模型的建立及特征分析

目的 建立幽门螺杆菌(Hp)感染慢性阻塞性肺病(COPD)大鼠模型,探讨Hp感染在C()PD进展中的作用机制.方法 40只Wistar大鼠均分为双重造模组(Hp感染、烟熏、气管内滴入脂多糖)、COPD组(烟熏、气管内滴入脂多糖)、Hp感染组及对照组.检测各组大鼠肺功能、血清及支气管肺泡灌洗液中细胞因子、支气管肺组织Hp相关基因表达水平,并进行支气管肺组织Hp分离培养.结果 COPD组和双重造模组大鼠肺组织均符合COPD病理表现,且后者病理改变更为明显.COPD组、双重造模组大鼠肺功能均较对照组及Hp感染组显著下降(P值均＜0.05),且双重造模组肺功能改变较COPD组更为明显(P值均＜0.05).随胃内Hp定植密度增加,双重造模组大鼠吸气阻力、呼气阻力上升(r值分别=0.785和0.905),动态肺顺应性、呼气峰值流速、0.3s呼气容积占肺活量的比例下降(r值分别=-0.975、-0.959、-0.976).与对照组比较,其余各组大鼠血清及支气管肺泡灌洗液中细胞因子IL-6、IL-8、肿瘤坏死因子(TNF)-α水平均显著升高(P值均＜0.05),其中双重造模组升高最明显(P值均＜0.05).仅部分双重造模组大鼠支气管肺组织中扩增出Hp尿素酶相关蛋白(UreC)基因,各组均未分离培养出Hp及可疑菌落.结论 Hp不直接定植于支气管肺组织,而是通过提高COPD模型大鼠血清及支气管肺泡中细胞因子水平而加重炎性反应,并由此导致COPD模型大鼠肺功能恶化.     

糖尿病大鼠胃窦部CGRP,VIP神经免疫组织化学及图像分析

为了解糖尿病时胃肠道肽能神经的改变，应用免疫组织化学及图像分析法对糖尿病大鼠胃窦部ＣＧＲＰ、ＶＩＰ神经进行了观察和分析。     

Ontogeny of neurohormonal peptides, serotonin, and nitric oxide synthase in the gastrointestinal neuroendocrine system of the axolotl (Ambystoma mexicanum): an immunohistochemical analysis

The ontogeny of the neurohormonal peptides vasoactive intestinal polypeptide (VIP), neurotensin (NT), substance P (SP), calcitonin gene-related peptide (CGRP), gastrin/cholecystokinin (GAS/CCK), and somatostatin (SOM) as well as serotonin (SER) and nitric oxide synthase (NOS) was investigated in the gastrointestinal tract of the urodele Ambystoma mexicanum, the axolotl, using immunohistochemical techniques. The first regulatory substances to appear were SP, SOM, and SER that could be immunohistochemically detected up from stage 1. At early stage 2, VIP immunoreactivity was observed infrequently in enteric nerve fibers. With the onset of external feeding at late stage 2, SP-immunoreactive (IR) and SER-IR endocrine cells and VIP-IR nerve fibers were present throughout the gastrointestinal tract. Furthermore, in the small intestine NT-IR and GAS/CCK-IR endocrine cells appeared. At stage 3, SER immunoreactivity was observed not only in endocrine cells but also in nerve fibers. CGRP-IR and SP-IR nerve fibers were detectable at stage 4 and stage 5, respectively. From stage 5 on, a minority of the CGRP immunoreactivity occurred in SP-IR nerve fibers. NOS immunoreactivity did not appear before stage 6 when it was found infrequently in nerve fibers. Thus, several phases of development can be distinguished: (1) at the yolk sac stages only few regulatory substances are present. (2) At the onset of external feeding, all endocrine cell types investigated were readily detectable. Thus, the onset of external feeding seems to trigger the development of the gastrointestinal endocrine system. (3) The endocrine cells are first found in the proximal part of the gastrointestinal tract and later in higher numbers in the distal parts. (4) The dually distributed neurohormonal peptides and SER first appear in endocrine cells and later additionally in nerve fibers. Thus, the nerve fibers likely set up the fine regulation of gastrointestinal blood flow and motility.     

降钙素基因相关肽免疫反应纤维在大鼠心肌内的分布和密度

目的 观察降钙素基因相关肽免疫反应(CGRP-IR)纤维在大鼠心肌内的分布和密度，为心肌病的研究奠定形态学基础。方法 用免疫组织化学法显示大鼠心肌内的CGRP-IR纤维，计算其分布密度。结果在心房肌内和心室肌内均可见CGRP-IR纤维分布于心肌纤维之间，心房肌内CGRP-IR纤维的面积密度和数量密度均高于心室肌。结论 CGRP-IR纤维在大鼠心肌内分布广泛，其分布密度存在部位差异。     

Peptide-containing nerves in labial salivary glands in Sj?gren's syndrome.

OBJECTIVE. The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sj?gren's syndrome patients were compared with those in salivary glands from 7 healthy controls. METHODS. Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P. RESULTS. Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION. This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.     

Nitrinergic and peptidergic innervation of the human oesophagus.

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.     

胃电刺激对大鼠十二指肠部分肠神经递质释放的影响

背景：胃电刺激（GES）对胃动力的影响已引起广泛关注，但关于GES后十二指肠肌间丛神经及其递质的变化。目前所知尚少。目的：研究GES对大鼠十二指肠壁内乙酰胆碱（Ach）、一氧化氮（NO）、P物质（SP）和血管活性肠肽（VIP）释放的影响。方法：建立Wistar大鼠GES模型，将模型大鼠分为GES组（n=10）和对照组（n=6）。选用适宦的刺激参数控制GES组胃慢波，应用免疫组化方法结合图像分析技术分析十二指肠肌间神经丛胆碱能、NO能、SP能和VIP能神经活性的变化。结果：GES组十二指肠肌间神经丛胆碱乙酰转移酶（ChAT）、神经元划一氧化氮合酶（nNOS）免疫反应阳性纤维较对照组明显增多、染色增强。易见ChAT、nNOS免疫反应阳性神经节和阳性神经元细胞体；而SP、VIP免疫反应阳性纤维和末梢及其染色强度在GES后无明显变化。GES组肌删种经从ChAT、nNOS免疫反应阳性产物的平均光密度值显著高于对照组（P〈0．001），SP、VIP免疫反应阳性产物的平均光密度值则与对照绀无显著差异（P〉0．05）。结论：GES后大鼠十二指肠壁内Ach、NO释放增多，VIP、SP则无明显变化。     

Vasoactive intestinal polypeptide as mediator of asthma

Vasoactive intestinal polypeptide (VIP) is one of the most abundant, biologically active peptides found in the human lung. VIP is a likely neurotransmitter or neuromodulator of the inhibitory non-adrenergic non-cholinergic airway nervous system and influences many aspects of pulmonary biology. In human airways VIP-immunoreactive nerve fibres are present in the tracheobronchial airway smooth muscle layer, the walls of pulmonary and bronchial vessels and around submucosal glands. Next to its prominent bronchodilatory effects, VIP potently relaxes pulmonary vessels. The precise role of VIP in the pathogenesis of asthma is still uncertain. Although a therapy using the strong bronchodilatory effects of VIP would offer potential benefits, the rapid inactivation of the peptide by airway peptidases has prevented effective VIP-based drugs so far and non-peptide VIP-agonists did not reach clinical use.     

Patterns of innervation of vasoactive intestinal polypeptide, neuropeptide Y, and gastrin-releasing peptide immunoreactive nerves in the feline pancreas.

In this study, we performed a detailed analysis of the immunoreactive (IR) patterns and tissue distribution of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) in the feline pancreas by means of immunohistochemical and radioimmunological techniques. Immunoreactivity for each peptide is localized to varicose nerve fibers distributed throughout the exocrine and endocrine pancreas, with some differences in the density and pattern of fiber distribution. In the acinar and stromal compartments, VIP-IR processes have a higher density than NPY- and GRP-containing fibers, the latter being the least abundant. The vasculature receives a particularly prominent NPY innervation, while GRP- and VIP-IR fibers are found occasionally in association with blood vessels. Around ducts, NPY- and VIP-IR nerves are more numerous than those positive for GRP-IR, which are quite sparse. One of the most interesting findings of the present work is the visualization of all peptide-IRs both in neuronal cell bodies and fibers within the intrapancreatic ganglia. VIP-IR is observed in virtually all ganglion cells, while GRP- and NPY-IRs are seen in a few neuronal cells. VIP and NPY tissue levels are much higher than GRP concentrations in all regions of the pancreas. VIP content in the head and body is greater than in the tail. The morphological relationship of VIP-, NPY-, and GRP-IR fibers with different pancreatic structures is consistent with specific peptidergic neural inputs in the regulation of pancreatic functions.