AIMS To investigate the structure-activity relation- ship of PACAP on guinea pig gallbladder by using syn- thetic PACAP/VIP hybrid peptides. METHODS We synthesized the PACAP/VIP hybrid peptides by a simultaneous multi...AIMS To investigate the structure-activity relation- ship of PACAP on guinea pig gallbladder by using syn- thetic PACAP/VIP hybrid peptides. METHODS We synthesized the PACAP/VIP hybrid peptides by a simultaneous multiple solid-phase pep- tide synthesizer using the Fmoc strategy. The peptides were tested on the isolated guinea pig gallbladder us- ing an improved horizontal-type organ bath. RESULTS VIP induced relaxation of gallbladder smooth muscle strips,while PACAP27 contracted them. Positions 4,5,9 and 24～26 can be replaced without significant loss in activity. [Leu^(13)]-PACAP27, a substitution in the α-helix domain,also had no signifi- cant loss in activity (P>0.05). It was more potent than [Gly^8]-and [DAsp^8]-PACAP27 and could substi- tute peptides at position 21. Des-[His^1] and [Ala^6]- PACAP27 had no activity at 10^(-7) mol/L. [Gly^8]-, [DAsp^8]-,[Phe^(21)]- and [Pro^(21)]-PACAP27 at 10^(-7)mol/L were about 25% of PACAP27 at 10^(-7) mol/L (P< 0.05). CONCLUSIONS In conclusion,for the physiological action of PACAP in guinea pig gallbladder,the N-termi- nal disordered region is more important than another region.展开更多
基金Supported by Monbusho international scientific research programa grant from the Ministry of Education Science and Culture,Japsn to Dr.S.Naruse.
文摘AIMS To investigate the structure-activity relation- ship of PACAP on guinea pig gallbladder by using syn- thetic PACAP/VIP hybrid peptides. METHODS We synthesized the PACAP/VIP hybrid peptides by a simultaneous multiple solid-phase pep- tide synthesizer using the Fmoc strategy. The peptides were tested on the isolated guinea pig gallbladder us- ing an improved horizontal-type organ bath. RESULTS VIP induced relaxation of gallbladder smooth muscle strips,while PACAP27 contracted them. Positions 4,5,9 and 24～26 can be replaced without significant loss in activity. [Leu^(13)]-PACAP27, a substitution in the α-helix domain,also had no signifi- cant loss in activity (P>0.05). It was more potent than [Gly^8]-and [DAsp^8]-PACAP27 and could substi- tute peptides at position 21. Des-[His^1] and [Ala^6]- PACAP27 had no activity at 10^(-7) mol/L. [Gly^8]-, [DAsp^8]-,[Phe^(21)]- and [Pro^(21)]-PACAP27 at 10^(-7)mol/L were about 25% of PACAP27 at 10^(-7) mol/L (P< 0.05). CONCLUSIONS In conclusion,for the physiological action of PACAP in guinea pig gallbladder,the N-termi- nal disordered region is more important than another region.
