Open AccessContribution of prostaglandin E2 to bradykinin-induced contraction in rabbit urinary detrusor.
Author(s) -
Norimichi Nakahata,
Tomoyuki Ono,
Hironori Nakanishi
Publication year - 1987
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.43.351
Subject(s) - bradykinin , chemistry , endocrinology , medicine , cyclooxygenase , detrusor muscle , acetylcholine , contraction (grammar) , prostaglandin e2 , methysergide , muscle contraction , arachidonic acid , kallidin , prazosin , prostaglandin , serotonin , biochemistry , kinin , biology , urinary bladder , enzyme , antagonist , receptor
Bradykinin (100 pM to 1 microM) contracted the rabbit urinary detrusor in vitro. The sensitivity to bradykinin was about 1000 times higher than that to acetylcholine (ACh) on a molar basis. The contractile response to bradykinin was unaffected by atropine, diphenhydramine, FPL-55712, methysergide, prazosin or tetrodotoxin, indicating that the contraction was not mediated via the release of ACh, histamine, peptide leukotrienes, serotonin or catecholamine. The bradykinin-induced contraction was, however, inhibited by indomethacin (5 microM), a cyclooxygenase inhibitor. Caffeic acid (10 microM), a lipoxygenase inhibitor, did not affect the contraction. Bradykinin (1 nM to 100 nM) stimulated the release of prostaglandin E2 from the detrusor in a concentration-dependent manner, and the release was abolished by treatment with indomethacin (5 microM). Prostaglandin (PG) E2 contracted the urinary detrusor with an EC50 of about 0.1 microM. Adenosine 5'-triphosphate (ATP), a stimulator of PG synthesis, also contracted the muscle with an EC50 of about 100 microM. [14C]Arachidonic acid was converted to PGE2 and F2 alpha when it was incubated with the 700 X g supernatant of the muscle homogenate. However, neither bradykinin nor ATP stimulated the PG synthesis in the supernatant. These results showed that bradykinin and ATP did not affect the cyclooxygenase and/or PG degradation system. On the other hand, when the intact detrusor muscle was incubated with [14C]arachidonic acid, bradykinin and ATP stimulated the PG synthesis, and the stimulated synthesis was inhibited by indomethacin. Mepacrine, a phospholipase A2 inhibitor, more potently inhibited the bradykinin- and ATP-induced contractions than the ACh-induced one.(ABSTRACT TRUNCATED AT 250 WORDS)