| Summary: | 碩士 === 國立東華大學 === 生命科學系 === 101 === Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to a neuropeptide substances involved in the regulation of gastrointestinal motility and endocrine digestive system. PACAP causes the lower esophageal sphincter relaxation in human and rat gastric antral muscle, and guinea pig gallbladder contraction. However, the response of human gallbladder muscle to PACAP remains unclear. This study was conducted to investigate the effects of PACAP on the human gallbladder muscle strip as compared with guinea pig gallbladder. The PACAP27 caused relaxation in human gallbladder with dose-dependent manner whereas muscle contraction was found in guinea pig gallbladder. (Ala11, 22, 28) VIP-VPAC1 selective peptide agonists and Bay 55-9837-VPAC2 selective peptide agonist could stimulate the muscle relaxation. In contrast PG97-269-VPAC1 receptor antagonist showed to inhibit the PACAP27-induced muscle relaxation. It is shown that the M65-PAC1 receptor antagonist did not inhibit the relaxation of gallbladder strip induced by PACAP27. Furthermore the experiment was found the tetrodotoxin-insensitive relaxation of human gallbladder. Using various inhibitors including L-NNA (NO), KT-5823 (cGMP protein kinase), KT-5720 (cAMP protein kinase) and iberiodotoxin (K+ blocker) to test the effect of relaxation, the results indicated that cGMP and cAMP protein kinase inhibitors caused the significant inhibition, implying that the human gallbladder muscle relaxation of PACAP27 stimulation might act on the VPAC1 and VPAC2 receptor mediated by cGMP and cAMP coupled with K+ ion channels. Furthermore, the existence of VPAC1 and VPAC2 in the human gallbladder muscle identified by RT-PCR and further experiment revealed the no significant difference of VPAC1 and VPAC2 in liver cancer with chronic cholecystitis and chronic cholecystitis. PACAP27 has the potential to be explored as a drug for treating the movement of gallbladder muscle.
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