Greaves R R, O'Donnell L J, Battistini B, Forget M A, Farthing M J
Digestive Diseases Research Centre, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Eur J Gastroenterol Hepatol. 2000 Nov;12(11):1181-4. doi: 10.1097/00042737-200012110-00003.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a recently identified member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. Like VIP, PACAP is largely inhibitory in the gastrointestinal tract. The aim of our work was to characterize the effects of PACAP on both contraction and relaxation of guinea pig gallbladder (GPGB) muscle.
Gallbladder muscle strips were obtained from male Dunkin-Hartley guinea pigs (250-350 g). Isometric tension was measured in strips suspended in gassed (95% O2, 5% CO2) Krebs' solution at 37 degrees C and equilibrated for 60 min. Cumulative additions of VIP or PACAP (10(-9)-10(-6) mol/l) were performed with strips at basal tone or with strips pre-contracted with cholecystokinin-octapeptide (CCK-8).
VIP had no effect on basal tone, in contrast with PACAP which produced concentration-dependent contraction to a maximum of 57.9 +/- 24.3% of control (CCK 3 x 10(-7) mol/l). The highest concentration (10(-6) mol/l) of VIP produced a 32 +/- 6% relaxation of 3 x 10(-9) mol/l CCK-8-contracted GPGB. With 3 x 10(-8) mol/l CCK-contracted GPGB strips, VIP produced a 26.7 +/- 6.6% relaxation. PACAP produced a further concentration-dependent contraction of 3 x 10(-9) mol/l CCK-contracted strips which reached 17.5 +/- 9.9% at the maximal concentration used (10(-6) mol/l). PACAP produced a concentration-dependent relaxation of 3 x 10(-8) mol/l CCK-contracted strips which reached a maximum relaxation of 19 +/- 5% of the control.
PACAP has a dual effect on guinea pig gallbladder motility in vitro, producing contraction in the basal state, and both contraction and relaxation in the CCK-contracted state. This is in contrast to the effects of VIP, a closely related peptide.
垂体腺苷酸环化酶激活多肽（PACAP）是最近发现的促胰液素/胰高血糖素/血管活性肠肽（VIP）家族成员。与VIP一样，PACAP在胃肠道中主要起抑制作用。我们研究的目的是确定PACAP对豚鼠胆囊（GPGB）肌肉收缩和舒张的影响。
从雄性Dunkin-Hartley豚鼠（250-350g）获取胆囊肌条。将肌条悬挂于37℃通气体（95%O₂，5%CO₂）的Krebs液中，测量等长张力，并平衡60分钟。对处于基础张力的肌条或用八肽胆囊收缩素（CCK-8）预收缩的肌条累积添加VIP或PACAP（10⁻⁹-10⁻⁶mol/L）。
VIP对基础张力无影响，而PACAP产生浓度依赖性收缩，最大收缩幅度达对照（CCK 3×10⁻⁷mol/L）的57.9±24.3%。VIP最高浓度（10⁻⁶mol/L）可使3×10⁻⁹mol/L CCK-8收缩的GPGB舒张32±6%。对于3×10⁻⁸mol/L CCK收缩的GPGB肌条，VIP产生26.7±6.6%的舒张。PACAP使3×10⁻⁹mol/L CCK收缩的肌条进一步产生浓度依赖性收缩，在所用最大浓度（10⁻⁶mol/L）时达到17.5±9.9%。PACAP使3×10⁻⁸mol/L CCK收缩的肌条产生浓度依赖性舒张，最大舒张幅度达对照的19±5%。
PACAP对豚鼠胆囊体外运动有双重作用，在基础状态下产生收缩，在CCK收缩状态下产生收缩和舒张。这与密切相关的肽VIP的作用相反。
