Proteinase-activated receptor-1 (PAR₁) and PAR₂ but not PAR₄ mediate contraction in human and guinea-pig gallbladders

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.