Response to isoprenaline of rabbit detrusor muscle following exposure to 5, 8, 11, 14 eicosatetraynoic acid. Role of prostanoids on beta-adrenergic-evoked response.
1. Incubation with indomethacin or ibuprofen causes a fall in basal tone and inhibits isoprenaline-evoked response in rabbit detrusor muscle strips. To ascertain whether this is due to cyclo-oxygenase inhibition, we investigated the influence on beta-adrenoceptor response of 5, 8, 11, 14 eicosatetraynoic acid (ETYA) which, unlike nonsteroidal anti-inflammatory drugs, has no action in vitro other than cyclo-oxygenase inhibition. 2. Incubation of detrusor strips with ETYA (7 or 14 microM) for 60 min significantly reduced tissue response to isoprenaline by an extent similar to that induced by indomethacin, but only slightly affected basal tone. 3. In tissues preincubated with indomethacin, the addition of PGE2 or PGE1 to restore basal tone, completely re-established isoprenaline-evoked responses. 4. Our findings in rabbit detrusor strips show that inhibition of cyclo-oxygenase and of prostanoid production is the main mechanism involved in lowered beta-adrenoceptor evoked response. 5. In addition, these findings strengthen the conviction that ibuprofen and indomethacin act largely through mechanisms other than inhibition of prostanoid production.
Bolle
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P
Department of Pharmacology and Phisiology, School of Pharmacy, University of Rome La Sapienza, Italy.
Fidanza
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S
Tucci
P
P
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D005071:Evoked Potentials; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D000527:Alprostadil; D015232:Dinoprostone; D007545:Isoproterenol; D007052:Ibuprofen; D007213:Indomethacin