Proteinase-activated receptor-1 (PAR1) and PAR2 mediate contraction in the guinea-pig gallbladder. To investigate and compare the effects mediated by PARs in the human gallbladder with those in the guinea-pig gallbladder, we measured contractions of isolated human and guinea-pig gallbladder strips caused by PAR agonists. Results in human were similar to those in guinea-pig gallbladder. The PAR1 agonists, thrombin, TFLLR-NH2 and SFLLRN-NH2, as well as the PAR2 agonists, trypsin, SLIGKV-NH2 and SLIGRL-NH 2, caused contraction in both human and guinea-pig gallbladders. These indicate the existence of PAR1 and PAR2 mediating gallbladder contraction. Furthermore, the existence of PAR1 and PAR2 in the human gallbladder was confirmed by reverse transcription-polymerase chain reaction. In contrast, FSLLR-NH2, a PAR1 control peptide, and VKGILS-NH2, a PAR2 control peptide, as well as three PAR4 agonists, GYPGKF-NH 2, GYPGQV-NH2 and AYPGKF-NH2, did not cause any contraction or relaxation. The contractile responses to TFLLR-NH2, SFLLRN-NH2 and trypsin in both human and guinea-pig gallbladders were insensitive to atropine and tetrodotoxin, suggesting direct effects. These results demonstrate that, similar to the guinea-pig gallbladder, both PAR 1 and PAR2 but not PAR4 mediate muscle contraction in the human gallbladder. PAR1 and PAR2 may play important roles in the control of both human and guinea-pig gallbladder motility.
- Proteinase-activated receptor
ASJC Scopus subject areas
- Endocrine and Autonomic Systems