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.
O'Riordan
A M
AM
Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Shelbourne Road, Dublin 4, Ireland.
Quinn
T
T
Baird
A W
AW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002413:Cations, Divalent; D003470:Culture Media; D015232:Dinoprostone / Q000378:metabolism*; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D003470:Culture Media; D007093:Imidazoles; D010894:Piroxicam; D019284:Thapsigargin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium