Bradykinin-induced contraction is inhibited by tiaramide, an anti-inflammatory drug, with an inhibition of increase in intracellular free calcium.
The mechanism of bradykinin-induced contraction in rabbit urinary detrusor was investigated using an anti-inflammatory drug, tiaramide. The contraction as well as prostaglandin (PG) E2 release induced by bradykinin was abolished by treatment with indomethacin, indicating that the contraction was mediated by PGs. The accumulation of inositol phosphates (IP) by bradykinin was partly inhibited by treatment with indomethacin, suggesting that part of the IP accumulation was due to PGs. Although the remaining accumulation of IPs induced by bradykinin in the presence of indomethacin should elicit contraction in smooth muscle cells, indomethacin abolished bradykinin-induced contraction. The dissociation between indomethacin-induced inhibition of IP accumulation and contraction induced by bradykinin might be explained by the existence of PG-generating cells in addition to smooth muscle cells. Bradykinin stimulates phospholipase C, which leads to an increase in intracellular free Ca++, activation of phospholipase A2 and release of PGs in the PG-generating cells. The released PGs act on smooth muscle cells to elicit contractions via phospholipase C activation and Ca++ mobilization. Tiaramide inhibited the PGE2 release and contraction induced by bradykinin by reducing the arachidonic acid release from membrane phospholipid but did not have a direct effect on cyclo-oxygenase. Tiaramide reduced IP accumulation induced by bradykinin to an extent similar to indomethacin. However, tiaramide had no effect on IP accumulation induced by PGE2, although it potently inhibited the contraction induced by PGE2, which elicits contractions without affecting phospholipase A2. The rise in intracellular free Ca++ induced by PGE2 as well as bradykinin was inhibited by tiaramide.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D052160:Benzothiazoles; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism*; D015232:Dinoprostone; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D001743:Urinary Bladder / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D052160:Benzothiazoles; D007295:Inositol Phosphates; D010879:Piperazines; D011458:Prostaglandins E; D016718:Arachidonic Acid; C003468:tiaramide; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium