The differential effect of VIP and PACAP on guinea pig gallbladder in vitro

Objectives 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. Methods Gallbladder muscle strips were obtained from male Dunkin-Hartley guinea pigs (250-350 g). Isometric tension was measured in strips suspended in gassed (95% O 2 , 5% CO 2 ) Krebs' solution at 37°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). Results 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. Conclusions 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.