title: Proteinase-activated receptor-1 (PAR(1)) and PAR(2) but not PAR(4) mediate contraction in human and guinea-pig gallbladders.
abstract: Proteinase-activated receptor-1 (PAR(1)) and PAR(2) 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 PAR(1) agonists, thrombin, TFLLR-NH2 and SFLLRN-NH2, as well as the PAR(2) agonists, trypsin, SLIGKV-NH2 and SLIGRL-NH2, caused contraction in both human and guinea-pig gallbladders. These indicate the existence of PAR(1) and PAR(2) mediating gallbladder contraction. Furthermore, the existence of PAR(1) and PAR(2) in the human gallbladder was confirmed by reverse transcription-polymerase chain reaction. In contrast, FSLLR-NH2, a PAR(1) control peptide, and VKGILS-NH2, a PAR(2) control peptide, as well as three PAR(4) agonists, GYPGKF-NH2, 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 PAR(2) but not PAR(4) mediate muscle contraction in the human gallbladder. PAR(1) and PAR(2) may play important roles in the control of both human and guinea-pig gallbladder motility.
authors.affiliation: Department of Surgery, Graduate Institute of Medicine, Tzu Chi University and Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lee
authors.forename: S-C
authors.initials: SC
authors.lastname: Huang
mesh_terms: D000818:Animals; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D016473:Gallbladder Emptying / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D044463:Receptor, PAR-1 / Q000187:drug effects / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000187:drug effects / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014357:Trypsin; D013917:Thrombin; C112908:protease-activated receptor 4