Role of prostaglandin E(2) and Ca(2+) in bradykinin induced contractions of guinea-pig gallbladder in vitro.

In this study, we investigated the contribution of prostaglandin E(2) to bradykinin induced contractions of guinea-pig gallbladder in vitro and characterized the sources of activator Ca(2+) for the bradykinin mediated contractions. Contractions induced by bradykinin in guinea-pig gallbladder smooth muscle strips were significantly attenuated by the cyclooxygenase inhibitor piroxicam (10 microM). In the presence of piroxicam, a threshold concentration of prostaglandin E(2) (1 nM) significantly enhanced the contractile response to subsequent challenge with bradykinin. Contractile responses to bradykinin were abolished in a Ca(2+)-free medium plus EDTA. The inhibitor of receptor mediated Ca(2+) entry, SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride, 10-50 microM) dose dependently abolished the response to bradykinin, while this response was only partially attenuated by nifedipine (10-50 microM; a voltage-operated Ca(2+) channel antagonist). Thapsigargin (an inhibitor of the sarcoplasmic reticulum calcium ATP-ase pump, 1 microM) produced sustained contractions of guinea-pig gallbladder strips that were dependent on extracellular Ca(2+). After incubation of strips in a Ca(2+)-free medium with thapsigargin, replacement of Ca(2+) caused a large sustained contraction. We conclude that the contractile response of guinea-pig gallbladder to bradykinin is modulated by prostaglandin E(2). Bradykinin induced contractions of guinea-pig gallbladder are highly dependent on extracellular Ca(2+) which enters through store-operated Ca(2+) channels and partially through voltage-operated Ca(2+) channels.