Bradykinin B2 receptors mediate contraction in the normal and inflamed human gallbladder in vitro.
OBJECTIVE
The components of the kinin system, including kinongens, kininogenases, and B(2) and B(1) receptors, are expressed and activated during inflammation. Here, we investigated the expression of the kinin B(2) receptor messenger RNA, kininogen and kallikrein immunoreactivity, and the ability of kinins to contract control and inflamed gallbladders in vitro.


METHODS
Human gallbladders, obtained from patients undergoing cholecystectomy either for acute cholecystitis secondary to gallstone disease or during elective gastro-entero-pancreatic surgery (controls), were processed for reverse-transcription polymerase chain reaction analysis, kallikrein and kininogen immunohistochemistry, binding studies, and in vitro contractility studies.


RESULTS
Tissue expression of B(2) receptor messenger RNA and specific binding of [(3)H]-bradykinin increased significantly in acute cholecystitis compared to controls. Kallikrein immunoreactivity was detected in the epithelium and infiltrating leukocytes, whereas kininogen immunoreactivity in the lumen of blood vessels and interstitial space. Bradykinin contracted isolated strips of control and acute cholecystitis gallbladders. In acute cholecystitis tissue, efficacy of bradykinin was higher than that of control gallbladders and similar to that of cholecystokinin. The contraction induced by bradykinin was significantly attenuated by B(2) receptor antagonism but not by cyclooxygenase inhibition and B(1), muscarinic, or tachykinin receptor antagonism.


CONCLUSIONS
All the components of the kinin system are expressed in the human gallbladder. Bradykinin is a powerful spasmogen via B(2) receptor activation in the normal and, especially, in the inflamed human gallbladder.
Trevisani
Marcello
M
Department of Experimental Medicine and Clinical Medicine, Pharmacology Unit, University of Ferrara, Italy.
Amadesi
Silvia
S
Schmidlin
Fabien
F
Poblete
Maria T
MT
Bardella
Elisabetta
E
Maggiore
Barbara
B
Harrison
Selena
S
Figueroa
Carlos D
CD
Tognetto
Michele
M
Navarra
Giuseppe
G
Turini
Alessandro
A
Bunnett
Nigel W
NW
Geppetti
Pierangelo
P
De Giorgio
Roberto
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000502:physiology*; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D001549:Benzamides; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D018727:Muscarinic Antagonists; D010880:Piperidines; D011812:Quinuclidines; C120984:R 715; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014316:Tritium; C085215:SR 140333; C073839:SR 48968; D001285:Atropine; C065679:icatibant; C091554:SR 142801; D001920:Bradykinin; D007213:Indomethacin